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view spring_package/tmalign/TMalign.cpp @ 17:c790d25086dc draft
"planemo upload commit b0ede77caf410ab69043d33a44e190054024d340-dirty"
| author | guerler |
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| date | Wed, 28 Oct 2020 05:11:56 +0000 |
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/* TM-align: sequence-independent structure alignment of monomer proteins by * TM-score superposition. Please report issues to yangzhanglab@umich.edu * * References to cite: * Y Zhang, J Skolnick. Nucl Acids Res 33, 2302-9 (2005) * * DISCLAIMER: * Permission to use, copy, modify, and distribute the Software for any * purpose, with or without fee, is hereby granted, provided that the * notices on the head, the reference information, and this copyright * notice appear in all copies or substantial portions of the Software. * It is provided "as is" without express or implied warranty. * * ========================== * How to install the program * ========================== * The following command compiles the program in your Linux computer: * * g++ -static -O3 -ffast-math -lm -o TMalign TMalign.cpp * * The '-static' flag should be removed on Mac OS, which does not support * building static executables. * * ====================== * How to use the program * ====================== * You can run the program without argument to obtain the document. * Briefly, you can compare two structures by: * * ./TMalign structure1.pdb structure2.pdb * * ============== * Update history * ============== * 2012/01/24: A C/C++ code of TM-align was constructed by Jianyi Yang * 2016/05/21: Several updates of this program were made by Jianji Wu: * (1) fixed several compiling bugs * (2) made I/O of C/C++ version consistent with the Fortran version * (3) added outputs including full-atom and ligand structures * (4) added options of '-i', '-I' and '-m' * 2016/05/25: Fixed a bug on PDB file reading * 2018/06/04: Several updates were made by Chengxin Zhang, including * (1) Fixed bug in reading PDB files with negative residue index, * (2) Implemented the fTM-align algorithm (by the '-fast' option) * as described in R Dong, S Pan, Z Peng, Y Zhang, J Yang * (2018) Nucleic acids research. gky430. * (3) Included option to perform TM-align against a whole * folder of PDB files. A full list of options not available * in the Fortran version can be explored by TMalign -h * 2018/07/27: Added the -byresi option for TM-score superposition without * re-alignment as in TMscore and TMscore -c * 2018/08/07: Added the -dir option * 2018/08/14: Added the -split option * 2018/08/16: Added the -infmt1, -infmt2 options. * 2019/01/07: Added support for PDBx/mmCIF format. * 2019/02/09: Fixed asymmetric alignment bug. * 2019/03/17: Added the -cp option for circular permutation * 2019/07/23: Supported RasMol output by '-o' option * 2019/07/24: Fixed bug on PyMOL format output by '-o' option with mmCIF input * 2019/08/18: Fixed bug on RasMol format output file *_atm. Removed excessive * circular permutation alignment by -cp * 2019/08/20: Clarified PyMOL syntax. * 2019/08/22: Added four additional PyMOL scripts. */ #include <math.h> #include <stdio.h> #include <stdlib.h> #include <time.h> #include <string.h> #include <malloc/malloc.h> #include <sstream> #include <iostream> #include <iomanip> #include <fstream> #include <vector> #include <iterator> #include <algorithm> #include <string> #include <map> using namespace std; void print_version() { cout << "\n" " *********************************************************************\n" " * TM-align (Version 20190822): protein structure alignment *\n" " * References: Y Zhang, J Skolnick. Nucl Acids Res 33, 2302-9 (2005) *\n" " * Please email comments and suggestions to yangzhanglab@umich.edu *\n" " *********************************************************************" << endl; } void print_extra_help() { cout << "Additional options:\n" " -dir Perform all-against-all alignment among the list of PDB\n" " chains listed by 'chain_list' under 'chain_folder'. Note\n" " that the slash is necessary.\n" " $ TMalign -dir chain_folder/ chain_list\n" "\n" " -dir1 Use chain2 to search a list of PDB chains listed by 'chain1_list'\n" " under 'chain1_folder'. Note that the slash is necessary.\n" " $ TMalign -dir1 chain1_folder/ chain1_list chain2\n" "\n" " -dir2 Use chain1 to search a list of PDB chains listed by 'chain2_list'\n" " under 'chain2_folder'\n" " $ TMalign chain1 -dir2 chain2_folder/ chain2_list\n" "\n" " -suffix (Only when -dir1 and/or -dir2 are set, default is empty)\n" " add file name suffix to files listed by chain1_list or chain2_list\n" "\n" " -atom 4-character atom name used to represent a residue.\n" " Default is \" CA \" for proteins\n" " (note the spaces before and after CA).\n" "\n" " -ter Strings to mark the end of a chain\n" " 3: (default) TER, ENDMDL, END or different chain ID\n" " 2: ENDMDL, END, or different chain ID\n" " 1: ENDMDL or END\n" " 0: (default in the first C++ TMalign) end of file\n" "\n" " -split Whether to split PDB file into multiple chains\n" " 0: (default) treat the whole structure as one single chain\n" " 1: treat each MODEL as a separate chain (-ter should be 0)\n" " 2: treat each chain as a seperate chain (-ter should be <=1)\n" "\n" " -outfmt Output format\n" " 0: (default) full output\n" " 1: fasta format compact output\n" " 2: tabular format very compact output\n" " -1: full output, but without version or citation information\n" "\n" " -byresi Whether to assume residue index correspondence between the\n" " two structures.\n" " 0: (default) sequence independent alignment\n" " 1: (same as TMscore program) sequence-dependent superposition,\n" " i.e. align by residue index\n" " 2: (same as TMscore -c, should be used with -ter <=1)\n" " align by residue index and chain ID\n" " 3: (similar to TMscore -c, should be used with -ter <=1)\n" " align by residue index and order of chain\n" "\n" " -TMcut -1: (default) do not consider TMcut\n" " Values in [0.5,1): Do not proceed with TM-align for this\n" " structure pair if TM-score is unlikely to reach TMcut.\n" " TMcut is normalized is set by -a option:\n" " -2: normalized by longer structure length\n" " -1: normalized by shorter structure length\n" " 0: (default, same as F) normalized by second structure\n" " 1: same as T, normalized by average structure length\n" "\n" " -mirror Whether to align the mirror image of input structure\n" " 0: (default) do not align mirrored structure\n" " 1: align mirror of chain1 to origin chain2\n" "\n" " -het Whether to align residues marked as 'HETATM' in addition to 'ATOM '\n" " 0: (default) only align 'ATOM ' residues\n" " 1: align both 'ATOM ' and 'HETATM' residues\n" "\n" " -infmt1 Input format for chain1\n" " -infmt2 Input format for chain2\n" " -1: (default) automatically detect PDB or PDBx/mmCIF format\n" " 0: PDB format\n" " 1: SPICKER format\n" " 2: xyz format\n" " 3: PDBx/mmCIF format\n" <<endl; } void print_help(bool h_opt=false) { print_version(); cout << "\n" "Usage: TMalign PDB1.pdb PDB2.pdb [Options]\n" "\n" "Options:\n" " -u TM-score normalized by user assigned length (the same as -L)\n" " warning: it should be >= minimum length of the two structures\n" " otherwise, TM-score may be >1\n" "\n" " -a TM-score normalized by the average length of two structures\n" " T or F, (default F)\n" "\n" " -i Start with an alignment specified in fasta file 'align.txt'\n" "\n" " -I Stick to the alignment specified in 'align.txt'\n" "\n" " -m Output TM-align rotation matrix\n" "\n" " -d TM-score scaled by an assigned d0, e.g. 5 Angstroms\n" "\n" " -o Output the superposition to 'TM_sup*'\n" " $ TMalign PDB1.pdb PDB2.pdb -o TM_sup\n" " View superposed C-alpha traces of aligned regions by RasMol or PyMOL:\n" " $ rasmol -script TM_sup\n" " $ pymol -d @TM_sup.pml\n" " View superposed C-alpha traces of all regions:\n" " $ rasmol -script TM_sup_all\n" " $ pymol -d @TM_sup_all.pml\n" " View superposed full-atom structures of aligned regions:\n" " $ rasmol -script TM_sup_atm\n" " $ pymol -d @TM_sup_atm.pml\n" " View superposed full-atom structures of all regions:\n" " $ rasmol -script TM_sup_all_atm\n" " $ pymol -d @TM_sup_all_atm.pml\n" " View superposed full-atom structures and ligands of all regions\n" " $ rasmol -script TM_sup_all_atm_lig\n" " $ pymol -d @TM_sup_all_atm_lig.pml\n" "\n" " -fast Fast but slightly inaccurate alignment by fTM-align algorithm\n" "\n" " -cp Alignment with circular permutation\n" "\n" " -v Print the version of TM-align\n" "\n" " -h Print the full help message, including additional options\n" "\n" " (Options -u, -a, -d, -o will not change the final structure alignment)\n\n" "Example usages:\n" " TMalign PDB1.pdb PDB2.pdb\n" " TMalign PDB1.pdb PDB2.pdb -u 100 -d 5.0\n" " TMalign PDB1.pdb PDB2.pdb -a T -o PDB1.sup\n" " TMalign PDB1.pdb PDB2.pdb -i align.txt\n" " TMalign PDB1.pdb PDB2.pdb -m matrix.txt\n" " TMalign PDB1.pdb PDB2.pdb -fast\n" " TMalign PDB1.pdb PDB2.pdb -cp\n" <<endl; if (h_opt) print_extra_help(); exit(EXIT_SUCCESS); } /* Functions for the core TMalign algorithm, including the entry function * TMalign_main */ void PrintErrorAndQuit(const string sErrorString) { cout << sErrorString << endl; exit(1); } template <typename T> inline T getmin(const T &a, const T &b) { return b<a?b:a; } template <class A> void NewArray(A *** array, int Narray1, int Narray2) { *array=new A* [Narray1]; for(int i=0; i<Narray1; i++) *(*array+i)=new A [Narray2]; } template <class A> void DeleteArray(A *** array, int Narray) { for(int i=0; i<Narray; i++) if(*(*array+i)) delete [] *(*array+i); if(Narray) delete [] (*array); (*array)=NULL; } string AAmap(char A) { if (A=='A') return "ALA"; if (A=='B') return "ASX"; if (A=='C') return "CYS"; if (A=='D') return "ASP"; if (A=='E') return "GLU"; if (A=='F') return "PHE"; if (A=='G') return "GLY"; if (A=='H') return "HIS"; if (A=='I') return "ILE"; if (A=='K') return "LYS"; if (A=='L') return "LEU"; if (A=='M') return "MET"; if (A=='N') return "ASN"; if (A=='O') return "PYL"; if (A=='P') return "PRO"; if (A=='Q') return "GLN"; if (A=='R') return "ARG"; if (A=='S') return "SER"; if (A=='T') return "THR"; if (A=='U') return "SEC"; if (A=='V') return "VAL"; if (A=='W') return "TRP"; if (A=='Y') return "TYR"; if (A=='Z') return "GLX"; return "UNK"; } char AAmap(const string &AA) { if (AA.compare("ALA")==0 || AA.compare("DAL")==0) return 'A'; if (AA.compare("ASX")==0) return 'B'; if (AA.compare("CYS")==0 || AA.compare("DCY")==0) return 'C'; if (AA.compare("ASP")==0 || AA.compare("DAS")==0) return 'D'; if (AA.compare("GLU")==0 || AA.compare("DGL")==0) return 'E'; if (AA.compare("PHE")==0 || AA.compare("DPN")==0) return 'F'; if (AA.compare("GLY")==0) return 'G'; if (AA.compare("HIS")==0 || AA.compare("DHI")==0) return 'H'; if (AA.compare("ILE")==0 || AA.compare("DIL")==0) return 'I'; if (AA.compare("LYS")==0 || AA.compare("DLY")==0) return 'K'; if (AA.compare("LEU")==0 || AA.compare("DLE")==0) return 'L'; if (AA.compare("MET")==0 || AA.compare("MED")==0 || AA.compare("MSE")==0) return 'M'; if (AA.compare("ASN")==0 || AA.compare("DSG")==0) return 'N'; if (AA.compare("PYL")==0) return 'O'; if (AA.compare("PRO")==0 || AA.compare("DPR")==0) return 'P'; if (AA.compare("GLN")==0 || AA.compare("DGN")==0) return 'Q'; if (AA.compare("ARG")==0 || AA.compare("DAR")==0) return 'R'; if (AA.compare("SER")==0 || AA.compare("DSN")==0) return 'S'; if (AA.compare("THR")==0 || AA.compare("DTH")==0) return 'T'; if (AA.compare("SEC")==0) return 'U'; if (AA.compare("VAL")==0 || AA.compare("DVA")==0) return 'V'; if (AA.compare("TRP")==0 || AA.compare("DTR")==0) return 'W'; if (AA.compare("TYR")==0 || AA.compare("DTY")==0) return 'Y'; if (AA.compare("GLX")==0) return 'Z'; return 'X'; } /* split a long string into vectors by whitespace * line - input string * line_vec - output vector * delimiter - delimiter */ void split(const string &line, vector<string> &line_vec, const char delimiter=' ') { bool within_word = false; for (int pos=0;pos<line.size();pos++) { if (line[pos]==delimiter) { within_word = false; continue; } if (!within_word) { within_word = true; line_vec.push_back(""); } line_vec.back()+=line[pos]; } } /* split a long string into vectors by whitespace, return both whitespaces * and non-whitespaces * line - input string * line_vec - output vector * space_vec - output vector * delimiter - delimiter */ void split_white(const string &line, vector<string> &line_vec, vector<string>&white_vec, const char delimiter=' ') { bool within_word = false; for (int pos=0;pos<line.size();pos++) { if (line[pos]==delimiter) { if (within_word==true) { white_vec.push_back(""); within_word = false; } white_vec.back()+=delimiter; } else { if (within_word==false) { line_vec.push_back(""); within_word = true; } line_vec.back()+=line[pos]; } } } size_t get_PDB_lines(const string filename, vector<vector<string> >&PDB_lines, vector<string> &chainID_list, vector<int> &mol_vec, const int ter_opt, const int infmt_opt, const string atom_opt, const int split_opt, const int het_opt) { size_t i=0; // resi i.e. atom index string line; char chainID=0; string resi=""; bool select_atom=false; size_t model_idx=0; vector<string> tmp_str_vec; ifstream fin; fin.open(filename.c_str()); if (infmt_opt==0||infmt_opt==-1) // PDB format { while (fin.good()) { getline(fin, line); if (infmt_opt==-1 && line.compare(0,5,"loop_")==0) // PDBx/mmCIF return get_PDB_lines(filename,PDB_lines,chainID_list, mol_vec, ter_opt, 3, atom_opt, split_opt,het_opt); if (i > 0) { if (ter_opt>=1 && line.compare(0,3,"END")==0) break; else if (ter_opt>=3 && line.compare(0,3,"TER")==0) break; } if (split_opt && line.compare(0,3,"END")==0) chainID=0; if ((line.compare(0, 6, "ATOM ")==0 || (line.compare(0, 6, "HETATM")==0 && het_opt)) && line.size()>=54 && (line[16]==' ' || line[16]=='A')) { if (atom_opt=="auto") select_atom=(line.compare(12,4," CA ")==0); else select_atom=(line.compare(12,4,atom_opt)==0); if (select_atom) { if (!chainID) { chainID=line[21]; model_idx++; stringstream i8_stream; i=0; if (split_opt==2) // split by chain { if (chainID==' ') { if (ter_opt>=1) i8_stream << ":_"; else i8_stream<<':'<<model_idx<<":_"; } else { if (ter_opt>=1) i8_stream << ':' << chainID; else i8_stream<<':'<<model_idx<<':'<<chainID; } chainID_list.push_back(i8_stream.str()); } else if (split_opt==1) // split by model { i8_stream << ':' << model_idx; chainID_list.push_back(i8_stream.str()); } PDB_lines.push_back(tmp_str_vec); mol_vec.push_back(0); } else if (ter_opt>=2 && chainID!=line[21]) break; if (split_opt==2 && chainID!=line[21]) { chainID=line[21]; i=0; stringstream i8_stream; if (chainID==' ') { if (ter_opt>=1) i8_stream << ":_"; else i8_stream<<':'<<model_idx<<":_"; } else { if (ter_opt>=1) i8_stream << ':' << chainID; else i8_stream<<':'<<model_idx<<':'<<chainID; } chainID_list.push_back(i8_stream.str()); PDB_lines.push_back(tmp_str_vec); mol_vec.push_back(0); } if (resi==line.substr(22,5)) cerr<<"Warning! Duplicated residue "<<resi<<endl; resi=line.substr(22,5); // including insertion code PDB_lines.back().push_back(line); if (line[17]==' ' && (line[18]=='D'||line[18]==' ')) mol_vec.back()++; else mol_vec.back()--; i++; } } } } else if (infmt_opt==1) // SPICKER format { int L=0; float x,y,z; stringstream i8_stream; while (fin.good()) { fin >>L>>x>>y>>z; getline(fin, line); if (!fin.good()) break; model_idx++; stringstream i8_stream; i8_stream << ':' << model_idx; chainID_list.push_back(i8_stream.str()); PDB_lines.push_back(tmp_str_vec); mol_vec.push_back(0); for (i=0;i<L;i++) { fin >>x>>y>>z; i8_stream<<"ATOM "<<setw(4)<<i+1<<" CA UNK "<<setw(4) <<i+1<<" "<<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x<<setw(8)<<y<<setw(8)<<z; line=i8_stream.str(); i8_stream.str(string()); PDB_lines.back().push_back(line); } getline(fin, line); } } else if (infmt_opt==2) // xyz format { int L=0; char A; stringstream i8_stream; while (fin.good()) { getline(fin, line); L=atoi(line.c_str()); getline(fin, line); for (i=0;i<line.size();i++) if (line[i]==' '||line[i]=='\t') break; if (!fin.good()) break; chainID_list.push_back(':'+line.substr(0,i)); PDB_lines.push_back(tmp_str_vec); mol_vec.push_back(0); for (i=0;i<L;i++) { getline(fin, line); i8_stream<<"ATOM "<<setw(4)<<i+1<<" CA " <<AAmap(line[0])<<" "<<setw(4)<<i+1<<" " <<line.substr(2,8)<<line.substr(11,8)<<line.substr(20,8); line=i8_stream.str(); i8_stream.str(string()); PDB_lines.back().push_back(line); if (line[0]>='a' && line[0]<='z') mol_vec.back()++; // RNA else mol_vec.back()--; } } } else if (infmt_opt==3) // PDBx/mmCIF format { bool loop_ = false; // not reading following content map<string,int> _atom_site; int atom_site_pos; vector<string> line_vec; string alt_id="."; // alternative location indicator string asym_id="."; // this is similar to chainID, except that // chainID is char while asym_id is a string // with possibly multiple char string prev_asym_id=""; string AA=""; // residue name string atom=""; string prev_resi=""; string model_index=""; // the same as model_idx but type is string stringstream i8_stream; while (fin.good()) { getline(fin, line); if (line.size()==0) continue; if (loop_) loop_ = line.compare(0,2,"# "); if (!loop_) { if (line.compare(0,5,"loop_")) continue; while(1) { if (fin.good()) getline(fin, line); else PrintErrorAndQuit("ERROR! Unexpected end of "+filename); if (line.size()) break; } if (line.compare(0,11,"_atom_site.")) continue; loop_=true; _atom_site.clear(); atom_site_pos=0; _atom_site[line.substr(11,line.size()-12)]=atom_site_pos; while(1) { if (fin.good()) getline(fin, line); else PrintErrorAndQuit("ERROR! Unexpected end of "+filename); if (line.size()==0) continue; if (line.compare(0,11,"_atom_site.")) break; _atom_site[line.substr(11,line.size()-12)]=++atom_site_pos; } if (_atom_site.count("group_PDB")* _atom_site.count("label_atom_id")* _atom_site.count("label_comp_id")* (_atom_site.count("auth_asym_id")+ _atom_site.count("label_asym_id"))* (_atom_site.count("auth_seq_id")+ _atom_site.count("label_seq_id"))* _atom_site.count("Cartn_x")* _atom_site.count("Cartn_y")* _atom_site.count("Cartn_z")==0) { loop_ = false; cerr<<"Warning! Missing one of the following _atom_site data items: group_PDB, label_atom_id, label_atom_id, auth_asym_id/label_asym_id, auth_seq_id/label_seq_id, Cartn_x, Cartn_y, Cartn_z"<<endl; continue; } } line_vec.clear(); split(line,line_vec); if (line_vec[_atom_site["group_PDB"]]!="ATOM" && (het_opt==0 || line_vec[_atom_site["group_PDB"]]!="HETATM")) continue; alt_id="."; if (_atom_site.count("label_alt_id")) // in 39.4 % of entries alt_id=line_vec[_atom_site["label_alt_id"]]; if (alt_id!="." && alt_id!="A") continue; atom=line_vec[_atom_site["label_atom_id"]]; if (atom[0]=='"') atom=atom.substr(1); if (atom.size() && atom[atom.size()-1]=='"') atom=atom.substr(0,atom.size()-1); if (atom.size()==0) continue; if (atom.size()==1) atom=" "+atom+" "; else if (atom.size()==2) atom=" "+atom+" "; // wrong for sidechain H else if (atom.size()==3) atom=" "+atom; else if (atom.size()>=5) continue; AA=line_vec[_atom_site["label_comp_id"]]; // residue name if (AA.size()==1) AA=" "+AA; else if (AA.size()==2) AA=" " +AA; else if (AA.size()>=4) continue; if (atom_opt=="auto") select_atom=(atom==" CA "); else select_atom=(atom==atom_opt); if (!select_atom) continue; if (_atom_site.count("auth_asym_id")) asym_id=line_vec[_atom_site["auth_asym_id"]]; else asym_id=line_vec[_atom_site["label_asym_id"]]; if (asym_id==".") asym_id=" "; if (_atom_site.count("pdbx_PDB_model_num") && model_index!=line_vec[_atom_site["pdbx_PDB_model_num"]]) { model_index=line_vec[_atom_site["pdbx_PDB_model_num"]]; if (PDB_lines.size() && ter_opt>=1) break; if (PDB_lines.size()==0 || split_opt>=1) { PDB_lines.push_back(tmp_str_vec); mol_vec.push_back(0); prev_asym_id=asym_id; if (split_opt==1 && ter_opt==0) chainID_list.push_back( ':'+model_index); else if (split_opt==2 && ter_opt==0) chainID_list.push_back(':'+model_index+':'+asym_id); else if (split_opt==2 && ter_opt==1) chainID_list.push_back(':'+asym_id); } } if (prev_asym_id!=asym_id) { if (prev_asym_id!="" && ter_opt>=2) break; if (split_opt>=2) { PDB_lines.push_back(tmp_str_vec); mol_vec.push_back(0); if (split_opt==1 && ter_opt==0) chainID_list.push_back( ':'+model_index); else if (split_opt==2 && ter_opt==0) chainID_list.push_back(':'+model_index+':'+asym_id); else if (split_opt==2 && ter_opt==1) chainID_list.push_back(':'+asym_id); } } if (prev_asym_id!=asym_id) prev_asym_id=asym_id; if (AA[0]==' ' && (AA[1]=='D'||AA[1]==' ')) mol_vec.back()++; else mol_vec.back()--; if (_atom_site.count("auth_seq_id")) resi=line_vec[_atom_site["auth_seq_id"]]; else resi=line_vec[_atom_site["label_seq_id"]]; if (_atom_site.count("pdbx_PDB_ins_code") && line_vec[_atom_site["pdbx_PDB_ins_code"]]!="?") resi+=line_vec[_atom_site["pdbx_PDB_ins_code"]][0]; else resi+=" "; if (prev_resi==resi) cerr<<"Warning! Duplicated residue "<<resi<<endl; prev_resi=resi; i++; i8_stream<<"ATOM " <<setw(5)<<i<<" "<<atom<<" "<<AA<<" "<<asym_id[0] <<setw(5)<<resi.substr(0,5)<<" " <<setw(8)<<line_vec[_atom_site["Cartn_x"]] <<setw(8)<<line_vec[_atom_site["Cartn_y"]] <<setw(8)<<line_vec[_atom_site["Cartn_z"]]; PDB_lines.back().push_back(i8_stream.str()); i8_stream.str(string()); } _atom_site.clear(); line_vec.clear(); alt_id.clear(); asym_id.clear(); AA.clear(); } fin.close(); line.clear(); if (!split_opt) chainID_list.push_back(""); return PDB_lines.size(); } /* read fasta file from filename. sequence is stored into FASTA_lines * while sequence name is stored into chainID_list. * if ter_opt >=1, only read the first sequence. * if ter_opt ==0, read all sequences. * if split_opt >=1 and ter_opt ==0, each sequence is a separate entry. * if split_opt ==0 and ter_opt ==0, all sequences are combined into one */ size_t get_FASTA_lines(const string filename, vector<vector<string> >&FASTA_lines, vector<string> &chainID_list, vector<int> &mol_vec, const int ter_opt=3, const int split_opt=0) { string line; vector<string> tmp_str_vec; int l; ifstream fin; fin.open(filename.c_str()); while (fin.good()) { getline(fin, line); if (line.size()==0 || line[0]=='#') continue; if (line[0]=='>') { if (FASTA_lines.size()) { if (ter_opt) break; if (split_opt==0) continue; } FASTA_lines.push_back(tmp_str_vec); FASTA_lines.back().push_back(""); mol_vec.push_back(0); if (ter_opt==0 && split_opt) { line[0]=':'; chainID_list.push_back(line); } else chainID_list.push_back(""); } else { FASTA_lines.back()[0]+=line; for (l=0;l<line.size();l++) mol_vec.back()+= ('a'<=line[l] && line[l]<='z')-('A'<=line[l] && line[l]<='Z'); } } line.clear(); fin.close(); return FASTA_lines.size(); } /* extract pairwise sequence alignment from residue index vectors, * assuming that "sequence" contains two empty strings. * return length of alignment, including gap. */ int extract_aln_from_resi(vector<string> &sequence, char *seqx, char *seqy, const vector<string> resi_vec1, const vector<string> resi_vec2, const int byresi_opt) { sequence.clear(); sequence.push_back(""); sequence.push_back(""); int i1=0; // positions in resi_vec1 int i2=0; // positions in resi_vec2 int xlen=resi_vec1.size(); int ylen=resi_vec2.size(); map<char,int> chainID_map1; map<char,int> chainID_map2; if (byresi_opt==3) { vector<char> chainID_vec; char chainID; int i; for (i=0;i<xlen;i++) { chainID=resi_vec1[i][5]; if (!chainID_vec.size()|| chainID_vec.back()!=chainID) { chainID_vec.push_back(chainID); chainID_map1[chainID]=chainID_vec.size(); } } chainID_vec.clear(); for (i=0;i<ylen;i++) { chainID=resi_vec2[i][5]; if (!chainID_vec.size()|| chainID_vec.back()!=chainID) { chainID_vec.push_back(chainID); chainID_map2[chainID]=chainID_vec.size(); } } chainID_vec.clear(); } while(i1<xlen && i2<ylen) { if ((byresi_opt<=2 && resi_vec1[i1]==resi_vec2[i2]) || (byresi_opt==3 && resi_vec1[i1].substr(0,5)==resi_vec2[i2].substr(0,5) && chainID_map1[resi_vec1[i1][5]]==chainID_map2[resi_vec2[i2][5]])) { sequence[0]+=seqx[i1++]; sequence[1]+=seqy[i2++]; } else if (atoi(resi_vec1[i1].substr(0,4).c_str())<= atoi(resi_vec2[i2].substr(0,4).c_str())) { sequence[0]+=seqx[i1++]; sequence[1]+='-'; } else { sequence[0]+='-'; sequence[1]+=seqy[i2++]; } } chainID_map1.clear(); chainID_map2.clear(); return sequence[0].size(); } int read_PDB(const vector<string> &PDB_lines, double **a, char *seq, vector<string> &resi_vec, const int byresi_opt) { int i; for (i=0;i<PDB_lines.size();i++) { a[i][0] = atof(PDB_lines[i].substr(30, 8).c_str()); a[i][1] = atof(PDB_lines[i].substr(38, 8).c_str()); a[i][2] = atof(PDB_lines[i].substr(46, 8).c_str()); seq[i] = AAmap(PDB_lines[i].substr(17, 3)); if (byresi_opt>=2) resi_vec.push_back(PDB_lines[i].substr(22,5)+ PDB_lines[i][21]); if (byresi_opt==1) resi_vec.push_back(PDB_lines[i].substr(22,5)); } seq[i]='\0'; return i; } double dist(double x[3], double y[3]) { double d1=x[0]-y[0]; double d2=x[1]-y[1]; double d3=x[2]-y[2]; return (d1*d1 + d2*d2 + d3*d3); } double dot(double *a, double *b) { return (a[0] * b[0] + a[1] * b[1] + a[2] * b[2]); } void transform(double t[3], double u[3][3], double *x, double *x1) { x1[0]=t[0]+dot(&u[0][0], x); x1[1]=t[1]+dot(&u[1][0], x); x1[2]=t[2]+dot(&u[2][0], x); } void do_rotation(double **x, double **x1, int len, double t[3], double u[3][3]) { for(int i=0; i<len; i++) { transform(t, u, &x[i][0], &x1[i][0]); } } /* strip white space at the begining or end of string */ string Trim(const string &inputString) { string result = inputString; int idxBegin = inputString.find_first_not_of(" \n\r\t"); int idxEnd = inputString.find_last_not_of(" \n\r\t"); if (idxBegin >= 0 && idxEnd >= 0) result = inputString.substr(idxBegin, idxEnd + 1 - idxBegin); return result; } /* read user specified pairwise alignment from 'fname_lign' to 'sequence'. * This function should only be called by main function, as it will * terminate a program if wrong alignment is given */ void read_user_alignment(vector<string>&sequence, const string &fname_lign, const int i_opt) { if (fname_lign == "") PrintErrorAndQuit("Please provide a file name for option -i!"); // open alignment file int n_p = 0;// number of structures in alignment file string line; ifstream fileIn(fname_lign.c_str()); if (fileIn.is_open()) { while (fileIn.good()) { getline(fileIn, line); if (line.compare(0, 1, ">") == 0)// Flag for a new structure { if (n_p >= 2) break; sequence.push_back(""); n_p++; } else if (n_p > 0 && line!="") sequence.back()+=line; } fileIn.close(); } else PrintErrorAndQuit("ERROR! Alignment file does not exist."); if (n_p < 2) PrintErrorAndQuit("ERROR: Fasta format is wrong, two proteins should be included."); if (sequence[0].size() != sequence[1].size()) PrintErrorAndQuit("ERROR! FASTA file is wrong. The length in alignment should be equal for the two aligned proteins."); if (i_opt==3) { int aligned_resNum=0; for (int i=0;i<sequence[0].size();i++) aligned_resNum+=(sequence[0][i]!='-' && sequence[1][i]!='-'); if (aligned_resNum<3) PrintErrorAndQuit("ERROR! Superposition is undefined for <3 aligned residues."); } line.clear(); return; } /* read list of entries from 'name' to 'chain_list'. * dir_opt is the folder name (prefix). * suffix_opt is the file name extension (suffix_opt). * This function should only be called by main function, as it will * terminate a program if wrong alignment is given */ void file2chainlist(vector<string>&chain_list, const string &name, const string &dir_opt, const string &suffix_opt) { ifstream fp(name.c_str()); if (! fp.is_open()) PrintErrorAndQuit(("Can not open file: "+name+'\n').c_str()); string line; while (fp.good()) { getline(fp, line); if (! line.size()) continue; chain_list.push_back(dir_opt+Trim(line)+suffix_opt); } fp.close(); line.clear(); } /************************************************************************** Implemetation of Kabsch algoritm for finding the best rotation matrix --------------------------------------------------------------------------- x - x(i,m) are coordinates of atom m in set x (input) y - y(i,m) are coordinates of atom m in set y (input) n - n is number of atom pairs (input) mode - 0:calculate rms only (input) 1:calculate u,t only (takes medium) 2:calculate rms,u,t (takes longer) rms - sum of w*(ux+t-y)**2 over all atom pairs (output) u - u(i,j) is rotation matrix for best superposition (output) t - t(i) is translation vector for best superposition (output) **************************************************************************/ bool Kabsch(double **x, double **y, int n, int mode, double *rms, double t[3], double u[3][3]) { int i, j, m, m1, l, k; double e0, rms1, d, h, g; double cth, sth, sqrth, p, det, sigma; double xc[3], yc[3]; double a[3][3], b[3][3], r[3][3], e[3], rr[6], ss[6]; double sqrt3 = 1.73205080756888, tol = 0.01; int ip[] = { 0, 1, 3, 1, 2, 4, 3, 4, 5 }; int ip2312[] = { 1, 2, 0, 1 }; int a_failed = 0, b_failed = 0; double epsilon = 0.00000001; //initializtation *rms = 0; rms1 = 0; e0 = 0; double c1[3], c2[3]; double s1[3], s2[3]; double sx[3], sy[3], sz[3]; for (i = 0; i < 3; i++) { s1[i] = 0.0; s2[i] = 0.0; sx[i] = 0.0; sy[i] = 0.0; sz[i] = 0.0; } for (i = 0; i<3; i++) { xc[i] = 0.0; yc[i] = 0.0; t[i] = 0.0; for (j = 0; j<3; j++) { u[i][j] = 0.0; r[i][j] = 0.0; a[i][j] = 0.0; if (i == j) { u[i][j] = 1.0; a[i][j] = 1.0; } } } if (n<1) return false; //compute centers for vector sets x, y for (i = 0; i<n; i++) { for (j = 0; j < 3; j++) { c1[j] = x[i][j]; c2[j] = y[i][j]; s1[j] += c1[j]; s2[j] += c2[j]; } for (j = 0; j < 3; j++) { sx[j] += c1[0] * c2[j]; sy[j] += c1[1] * c2[j]; sz[j] += c1[2] * c2[j]; } } for (i = 0; i < 3; i++) { xc[i] = s1[i] / n; yc[i] = s2[i] / n; } if (mode == 2 || mode == 0) for (int mm = 0; mm < n; mm++) for (int nn = 0; nn < 3; nn++) e0 += (x[mm][nn] - xc[nn]) * (x[mm][nn] - xc[nn]) + (y[mm][nn] - yc[nn]) * (y[mm][nn] - yc[nn]); for (j = 0; j < 3; j++) { r[j][0] = sx[j] - s1[0] * s2[j] / n; r[j][1] = sy[j] - s1[1] * s2[j] / n; r[j][2] = sz[j] - s1[2] * s2[j] / n; } //compute determinat of matrix r det = r[0][0] * (r[1][1] * r[2][2] - r[1][2] * r[2][1])\ - r[0][1] * (r[1][0] * r[2][2] - r[1][2] * r[2][0])\ + r[0][2] * (r[1][0] * r[2][1] - r[1][1] * r[2][0]); sigma = det; //compute tras(r)*r m = 0; for (j = 0; j<3; j++) { for (i = 0; i <= j; i++) { rr[m] = r[0][i] * r[0][j] + r[1][i] * r[1][j] + r[2][i] * r[2][j]; m++; } } double spur = (rr[0] + rr[2] + rr[5]) / 3.0; double cof = (((((rr[2] * rr[5] - rr[4] * rr[4]) + rr[0] * rr[5])\ - rr[3] * rr[3]) + rr[0] * rr[2]) - rr[1] * rr[1]) / 3.0; det = det*det; for (i = 0; i<3; i++) e[i] = spur; if (spur>0) { d = spur*spur; h = d - cof; g = (spur*cof - det) / 2.0 - spur*h; if (h>0) { sqrth = sqrt(h); d = h*h*h - g*g; if (d<0.0) d = 0.0; d = atan2(sqrt(d), -g) / 3.0; cth = sqrth * cos(d); sth = sqrth*sqrt3*sin(d); e[0] = (spur + cth) + cth; e[1] = (spur - cth) + sth; e[2] = (spur - cth) - sth; if (mode != 0) {//compute a for (l = 0; l<3; l = l + 2) { d = e[l]; ss[0] = (d - rr[2]) * (d - rr[5]) - rr[4] * rr[4]; ss[1] = (d - rr[5]) * rr[1] + rr[3] * rr[4]; ss[2] = (d - rr[0]) * (d - rr[5]) - rr[3] * rr[3]; ss[3] = (d - rr[2]) * rr[3] + rr[1] * rr[4]; ss[4] = (d - rr[0]) * rr[4] + rr[1] * rr[3]; ss[5] = (d - rr[0]) * (d - rr[2]) - rr[1] * rr[1]; if (fabs(ss[0]) <= epsilon) ss[0] = 0.0; if (fabs(ss[1]) <= epsilon) ss[1] = 0.0; if (fabs(ss[2]) <= epsilon) ss[2] = 0.0; if (fabs(ss[3]) <= epsilon) ss[3] = 0.0; if (fabs(ss[4]) <= epsilon) ss[4] = 0.0; if (fabs(ss[5]) <= epsilon) ss[5] = 0.0; if (fabs(ss[0]) >= fabs(ss[2])) { j = 0; if (fabs(ss[0]) < fabs(ss[5])) j = 2; } else if (fabs(ss[2]) >= fabs(ss[5])) j = 1; else j = 2; d = 0.0; j = 3 * j; for (i = 0; i<3; i++) { k = ip[i + j]; a[i][l] = ss[k]; d = d + ss[k] * ss[k]; } //if( d > 0.0 ) d = 1.0 / sqrt(d); if (d > epsilon) d = 1.0 / sqrt(d); else d = 0.0; for (i = 0; i<3; i++) a[i][l] = a[i][l] * d; }//for l d = a[0][0] * a[0][2] + a[1][0] * a[1][2] + a[2][0] * a[2][2]; if ((e[0] - e[1]) >(e[1] - e[2])) { m1 = 2; m = 0; } else { m1 = 0; m = 2; } p = 0; for (i = 0; i<3; i++) { a[i][m1] = a[i][m1] - d*a[i][m]; p = p + a[i][m1] * a[i][m1]; } if (p <= tol) { p = 1.0; for (i = 0; i<3; i++) { if (p < fabs(a[i][m])) continue; p = fabs(a[i][m]); j = i; } k = ip2312[j]; l = ip2312[j + 1]; p = sqrt(a[k][m] * a[k][m] + a[l][m] * a[l][m]); if (p > tol) { a[j][m1] = 0.0; a[k][m1] = -a[l][m] / p; a[l][m1] = a[k][m] / p; } else a_failed = 1; }//if p<=tol else { p = 1.0 / sqrt(p); for (i = 0; i<3; i++) a[i][m1] = a[i][m1] * p; }//else p<=tol if (a_failed != 1) { a[0][1] = a[1][2] * a[2][0] - a[1][0] * a[2][2]; a[1][1] = a[2][2] * a[0][0] - a[2][0] * a[0][2]; a[2][1] = a[0][2] * a[1][0] - a[0][0] * a[1][2]; } }//if(mode!=0) }//h>0 //compute b anyway if (mode != 0 && a_failed != 1)//a is computed correctly { //compute b for (l = 0; l<2; l++) { d = 0.0; for (i = 0; i<3; i++) { b[i][l] = r[i][0] * a[0][l] + r[i][1] * a[1][l] + r[i][2] * a[2][l]; d = d + b[i][l] * b[i][l]; } //if( d > 0 ) d = 1.0 / sqrt(d); if (d > epsilon) d = 1.0 / sqrt(d); else d = 0.0; for (i = 0; i<3; i++) b[i][l] = b[i][l] * d; } d = b[0][0] * b[0][1] + b[1][0] * b[1][1] + b[2][0] * b[2][1]; p = 0.0; for (i = 0; i<3; i++) { b[i][1] = b[i][1] - d*b[i][0]; p += b[i][1] * b[i][1]; } if (p <= tol) { p = 1.0; for (i = 0; i<3; i++) { if (p<fabs(b[i][0])) continue; p = fabs(b[i][0]); j = i; } k = ip2312[j]; l = ip2312[j + 1]; p = sqrt(b[k][0] * b[k][0] + b[l][0] * b[l][0]); if (p > tol) { b[j][1] = 0.0; b[k][1] = -b[l][0] / p; b[l][1] = b[k][0] / p; } else b_failed = 1; }//if( p <= tol ) else { p = 1.0 / sqrt(p); for (i = 0; i<3; i++) b[i][1] = b[i][1] * p; } if (b_failed != 1) { b[0][2] = b[1][0] * b[2][1] - b[1][1] * b[2][0]; b[1][2] = b[2][0] * b[0][1] - b[2][1] * b[0][0]; b[2][2] = b[0][0] * b[1][1] - b[0][1] * b[1][0]; //compute u for (i = 0; i<3; i++) for (j = 0; j<3; j++) u[i][j] = b[i][0] * a[j][0] + b[i][1] * a[j][1] + b[i][2] * a[j][2]; } //compute t for (i = 0; i<3; i++) t[i] = ((yc[i] - u[i][0] * xc[0]) - u[i][1] * xc[1]) - u[i][2] * xc[2]; }//if(mode!=0 && a_failed!=1) }//spur>0 else //just compute t and errors { //compute t for (i = 0; i<3; i++) t[i] = ((yc[i] - u[i][0] * xc[0]) - u[i][1] * xc[1]) - u[i][2] * xc[2]; }//else spur>0 //compute rms for (i = 0; i<3; i++) { if (e[i] < 0) e[i] = 0; e[i] = sqrt(e[i]); } d = e[2]; if (sigma < 0.0) d = -d; d = (d + e[1]) + e[0]; if (mode == 2 || mode == 0) { rms1 = (e0 - d) - d; if (rms1 < 0.0) rms1 = 0.0; } *rms = rms1; return true; } /* Partial implementation of Needleman-Wunsch (NW) dymanamic programming for * global alignment. The three NWDP_TM functions below are not complete * implementation of NW algorithm because gap jumping in the standard Gotoh * algorithm is not considered. Since the gap opening and gap extension is * the same, this is not a problem. This code was exploited in TM-align * because it is about 1.5 times faster than a complete NW implementation. * Nevertheless, if gap openning != gap extension shall be implemented in * the future, the Gotoh algorithm must be implemented. In rare scenarios, * it is also possible to have asymmetric alignment (i.e. * TMalign A.pdb B.pdb and TMalign B.pdb A.pdb have different TM_A and TM_B * values) caused by the NWPD_TM implement. */ /* Input: score[1:len1, 1:len2], and gap_open * Output: j2i[1:len2] \in {1:len1} U {-1} * path[0:len1, 0:len2]=1,2,3, from diagonal, horizontal, vertical */ void NWDP_TM(double **score, bool **path, double **val, int len1, int len2, double gap_open, int j2i[]) { int i, j; double h, v, d; //initialization for(i=0; i<=len1; i++) { val[i][0]=0; //val[i][0]=i*gap_open; path[i][0]=false; //not from diagonal } for(j=0; j<=len2; j++) { val[0][j]=0; //val[0][j]=j*gap_open; path[0][j]=false; //not from diagonal j2i[j]=-1; //all are not aligned, only use j2i[1:len2] } //decide matrix and path for(i=1; i<=len1; i++) { for(j=1; j<=len2; j++) { d=val[i-1][j-1]+score[i][j]; //diagonal //symbol insertion in horizontal (= a gap in vertical) h=val[i-1][j]; if(path[i-1][j]) h += gap_open; //aligned in last position //symbol insertion in vertical v=val[i][j-1]; if(path[i][j-1]) v += gap_open; //aligned in last position if(d>=h && d>=v) { path[i][j]=true; //from diagonal val[i][j]=d; } else { path[i][j]=false; //from horizontal if(v>=h) val[i][j]=v; else val[i][j]=h; } } //for i } //for j //trace back to extract the alignment i=len1; j=len2; while(i>0 && j>0) { if(path[i][j]) //from diagonal { j2i[j-1]=i-1; i--; j--; } else { h=val[i-1][j]; if(path[i-1][j]) h +=gap_open; v=val[i][j-1]; if(path[i][j-1]) v +=gap_open; if(v>=h) j--; else i--; } } } /* Input: vectors x, y, rotation matrix t, u, scale factor d02, and gap_open * Output: j2i[1:len2] \in {1:len1} U {-1} * path[0:len1, 0:len2]=1,2,3, from diagonal, horizontal, vertical */ void NWDP_TM(bool **path, double **val, double **x, double **y, int len1, int len2, double t[3], double u[3][3], double d02, double gap_open, int j2i[]) { int i, j; double h, v, d; //initialization. use old val[i][0] and val[0][j] initialization //to minimize difference from TMalign fortran version for(i=0; i<=len1; i++) { val[i][0]=0; //val[i][0]=i*gap_open; path[i][0]=false; //not from diagonal } for(j=0; j<=len2; j++) { val[0][j]=0; //val[0][j]=j*gap_open; path[0][j]=false; //not from diagonal j2i[j]=-1; //all are not aligned, only use j2i[1:len2] } double xx[3], dij; //decide matrix and path for(i=1; i<=len1; i++) { transform(t, u, &x[i-1][0], xx); for(j=1; j<=len2; j++) { dij=dist(xx, &y[j-1][0]); d=val[i-1][j-1] + 1.0/(1+dij/d02); //symbol insertion in horizontal (= a gap in vertical) h=val[i-1][j]; if(path[i-1][j]) h += gap_open; //aligned in last position //symbol insertion in vertical v=val[i][j-1]; if(path[i][j-1]) v += gap_open; //aligned in last position if(d>=h && d>=v) { path[i][j]=true; //from diagonal val[i][j]=d; } else { path[i][j]=false; //from horizontal if(v>=h) val[i][j]=v; else val[i][j]=h; } } //for i } //for j //trace back to extract the alignment i=len1; j=len2; while(i>0 && j>0) { if(path[i][j]) //from diagonal { j2i[j-1]=i-1; i--; j--; } else { h=val[i-1][j]; if(path[i-1][j]) h +=gap_open; v=val[i][j-1]; if(path[i][j-1]) v +=gap_open; if(v>=h) j--; else i--; } } } /* This is the same as the previous NWDP_TM, except for the lack of rotation * Input: vectors x, y, scale factor d02, and gap_open * Output: j2i[1:len2] \in {1:len1} U {-1} * path[0:len1, 0:len2]=1,2,3, from diagonal, horizontal, vertical */ void NWDP_SE(bool **path, double **val, double **x, double **y, int len1, int len2, double d02, double gap_open, int j2i[]) { int i, j; double h, v, d; for(i=0; i<=len1; i++) { val[i][0]=0; path[i][0]=false; //not from diagonal } for(j=0; j<=len2; j++) { val[0][j]=0; path[0][j]=false; //not from diagonal j2i[j]=-1; //all are not aligned, only use j2i[1:len2] } double dij; //decide matrix and path for(i=1; i<=len1; i++) { for(j=1; j<=len2; j++) { dij=dist(&x[i-1][0], &y[j-1][0]); d=val[i-1][j-1] + 1.0/(1+dij/d02); //symbol insertion in horizontal (= a gap in vertical) h=val[i-1][j]; if(path[i-1][j]) h += gap_open; //aligned in last position //symbol insertion in vertical v=val[i][j-1]; if(path[i][j-1]) v += gap_open; //aligned in last position if(d>=h && d>=v) { path[i][j]=true; //from diagonal val[i][j]=d; } else { path[i][j]=false; //from horizontal if(v>=h) val[i][j]=v; else val[i][j]=h; } } //for i } //for j //trace back to extract the alignment i=len1; j=len2; while(i>0 && j>0) { if(path[i][j]) //from diagonal { j2i[j-1]=i-1; i--; j--; } else { h=val[i-1][j]; if(path[i-1][j]) h +=gap_open; v=val[i][j-1]; if(path[i][j-1]) v +=gap_open; if(v>=h) j--; else i--; } } } /* +ss * Input: secondary structure secx, secy, and gap_open * Output: j2i[1:len2] \in {1:len1} U {-1} * path[0:len1, 0:len2]=1,2,3, from diagonal, horizontal, vertical */ void NWDP_TM(bool **path, double **val, const char *secx, const char *secy, const int len1, const int len2, const double gap_open, int j2i[]) { int i, j; double h, v, d; //initialization for(i=0; i<=len1; i++) { val[i][0]=0; //val[i][0]=i*gap_open; path[i][0]=false; //not from diagonal } for(j=0; j<=len2; j++) { val[0][j]=0; //val[0][j]=j*gap_open; path[0][j]=false; //not from diagonal j2i[j]=-1; //all are not aligned, only use j2i[1:len2] } //decide matrix and path for(i=1; i<=len1; i++) { for(j=1; j<=len2; j++) { d=val[i-1][j-1] + 1.0*(secx[i-1]==secy[j-1]); //symbol insertion in horizontal (= a gap in vertical) h=val[i-1][j]; if(path[i-1][j]) h += gap_open; //aligned in last position //symbol insertion in vertical v=val[i][j-1]; if(path[i][j-1]) v += gap_open; //aligned in last position if(d>=h && d>=v) { path[i][j]=true; //from diagonal val[i][j]=d; } else { path[i][j]=false; //from horizontal if(v>=h) val[i][j]=v; else val[i][j]=h; } } //for i } //for j //trace back to extract the alignment i=len1; j=len2; while(i>0 && j>0) { if(path[i][j]) //from diagonal { j2i[j-1]=i-1; i--; j--; } else { h=val[i-1][j]; if(path[i-1][j]) h +=gap_open; v=val[i][j-1]; if(path[i][j-1]) v +=gap_open; if(v>=h) j--; else i--; } } } void parameter_set4search(const int xlen, const int ylen, double &D0_MIN, double &Lnorm, double &score_d8, double &d0, double &d0_search, double &dcu0) { //parameter initilization for searching: D0_MIN, Lnorm, d0, d0_search, score_d8 D0_MIN=0.5; dcu0=4.25; //update 3.85-->4.25 Lnorm=getmin(xlen, ylen); //normaliz TMscore by this in searching if (Lnorm<=19) //update 15-->19 d0=0.168; //update 0.5-->0.168 else d0=(1.24*pow((Lnorm*1.0-15), 1.0/3)-1.8); D0_MIN=d0+0.8; //this should be moved to above d0=D0_MIN; //update: best for search d0_search=d0; if (d0_search>8) d0_search=8; if (d0_search<4.5) d0_search=4.5; score_d8=1.5*pow(Lnorm*1.0, 0.3)+3.5; //remove pairs with dis>d8 during search & final } void parameter_set4final_C3prime(const double len, double &D0_MIN, double &Lnorm, double &d0, double &d0_search) { D0_MIN=0.3; Lnorm=len; //normaliz TMscore by this in searching if(Lnorm<=11) d0=0.3; else if(Lnorm>11&&Lnorm<=15) d0=0.4; else if(Lnorm>15&&Lnorm<=19) d0=0.5; else if(Lnorm>19&&Lnorm<=23) d0=0.6; else if(Lnorm>23&&Lnorm<30) d0=0.7; else d0=(0.6*pow((Lnorm*1.0-0.5), 1.0/2)-2.5); d0_search=d0; if (d0_search>8) d0_search=8; if (d0_search<4.5) d0_search=4.5; } void parameter_set4final(const double len, double &D0_MIN, double &Lnorm, double &d0, double &d0_search, const int mol_type) { if (mol_type>0) // RNA { parameter_set4final_C3prime(len, D0_MIN, Lnorm, d0, d0_search); return; } D0_MIN=0.5; Lnorm=len; //normaliz TMscore by this in searching if (Lnorm<=21) d0=0.5; else d0=(1.24*pow((Lnorm*1.0-15), 1.0/3)-1.8); if (d0<D0_MIN) d0=D0_MIN; d0_search=d0; if (d0_search>8) d0_search=8; if (d0_search<4.5) d0_search=4.5; } void parameter_set4scale(const int len, const double d_s, double &Lnorm, double &d0, double &d0_search) { d0=d_s; Lnorm=len; //normaliz TMscore by this in searching d0_search=d0; if (d0_search>8) d0_search=8; if (d0_search<4.5) d0_search=4.5; } // 1, collect those residues with dis<d; // 2, calculate TMscore int score_fun8( double **xa, double **ya, int n_ali, double d, int i_ali[], double *score1, int score_sum_method, const double Lnorm, const double score_d8, const double d0) { double score_sum=0, di; double d_tmp=d*d; double d02=d0*d0; double score_d8_cut = score_d8*score_d8; int i, n_cut, inc=0; while(1) { n_cut=0; score_sum=0; for(i=0; i<n_ali; i++) { di = dist(xa[i], ya[i]); if(di<d_tmp) { i_ali[n_cut]=i; n_cut++; } if(score_sum_method==8) { if(di<=score_d8_cut) score_sum += 1/(1+di/d02); } else score_sum += 1/(1+di/d02); } //there are not enough feasible pairs, reliefe the threshold if(n_cut<3 && n_ali>3) { inc++; double dinc=(d+inc*0.5); d_tmp = dinc * dinc; } else break; } *score1=score_sum/Lnorm; return n_cut; } int score_fun8_standard(double **xa, double **ya, int n_ali, double d, int i_ali[], double *score1, int score_sum_method, double score_d8, double d0) { double score_sum = 0, di; double d_tmp = d*d; double d02 = d0*d0; double score_d8_cut = score_d8*score_d8; int i, n_cut, inc = 0; while (1) { n_cut = 0; score_sum = 0; for (i = 0; i<n_ali; i++) { di = dist(xa[i], ya[i]); if (di<d_tmp) { i_ali[n_cut] = i; n_cut++; } if (score_sum_method == 8) { if (di <= score_d8_cut) score_sum += 1 / (1 + di / d02); } else { score_sum += 1 / (1 + di / d02); } } //there are not enough feasible pairs, reliefe the threshold if (n_cut<3 && n_ali>3) { inc++; double dinc = (d + inc*0.5); d_tmp = dinc * dinc; } else break; } *score1 = score_sum / n_ali; return n_cut; } double TMscore8_search(double **r1, double **r2, double **xtm, double **ytm, double **xt, int Lali, double t0[3], double u0[3][3], int simplify_step, int score_sum_method, double *Rcomm, double local_d0_search, double Lnorm, double score_d8, double d0) { int i, m; double score_max, score, rmsd; const int kmax=Lali; int k_ali[kmax], ka, k; double t[3]; double u[3][3]; double d; //iterative parameters int n_it=20; //maximum number of iterations int n_init_max=6; //maximum number of different fragment length int L_ini[n_init_max]; //fragment lengths, Lali, Lali/2, Lali/4 ... 4 int L_ini_min=4; if(Lali<L_ini_min) L_ini_min=Lali; int n_init=0, i_init; for(i=0; i<n_init_max-1; i++) { n_init++; L_ini[i]=(int) (Lali/pow(2.0, (double) i)); if(L_ini[i]<=L_ini_min) { L_ini[i]=L_ini_min; break; } } if(i==n_init_max-1) { n_init++; L_ini[i]=L_ini_min; } score_max=-1; //find the maximum score starting from local structures superposition int i_ali[kmax], n_cut; int L_frag; //fragment length int iL_max; //maximum starting postion for the fragment for(i_init=0; i_init<n_init; i_init++) { L_frag=L_ini[i_init]; iL_max=Lali-L_frag; i=0; while(1) { //extract the fragment starting from position i ka=0; for(k=0; k<L_frag; k++) { int kk=k+i; r1[k][0]=xtm[kk][0]; r1[k][1]=xtm[kk][1]; r1[k][2]=xtm[kk][2]; r2[k][0]=ytm[kk][0]; r2[k][1]=ytm[kk][1]; r2[k][2]=ytm[kk][2]; k_ali[ka]=kk; ka++; } //extract rotation matrix based on the fragment Kabsch(r1, r2, L_frag, 1, &rmsd, t, u); if (simplify_step != 1) *Rcomm = 0; do_rotation(xtm, xt, Lali, t, u); //get subsegment of this fragment d = local_d0_search - 1; n_cut=score_fun8(xt, ytm, Lali, d, i_ali, &score, score_sum_method, Lnorm, score_d8, d0); if(score>score_max) { score_max=score; //save the rotation matrix for(k=0; k<3; k++) { t0[k]=t[k]; u0[k][0]=u[k][0]; u0[k][1]=u[k][1]; u0[k][2]=u[k][2]; } } //try to extend the alignment iteratively d = local_d0_search + 1; for(int it=0; it<n_it; it++) { ka=0; for(k=0; k<n_cut; k++) { m=i_ali[k]; r1[k][0]=xtm[m][0]; r1[k][1]=xtm[m][1]; r1[k][2]=xtm[m][2]; r2[k][0]=ytm[m][0]; r2[k][1]=ytm[m][1]; r2[k][2]=ytm[m][2]; k_ali[ka]=m; ka++; } //extract rotation matrix based on the fragment Kabsch(r1, r2, n_cut, 1, &rmsd, t, u); do_rotation(xtm, xt, Lali, t, u); n_cut=score_fun8(xt, ytm, Lali, d, i_ali, &score, score_sum_method, Lnorm, score_d8, d0); if(score>score_max) { score_max=score; //save the rotation matrix for(k=0; k<3; k++) { t0[k]=t[k]; u0[k][0]=u[k][0]; u0[k][1]=u[k][1]; u0[k][2]=u[k][2]; } } //check if it converges if(n_cut==ka) { for(k=0; k<n_cut; k++) { if(i_ali[k]!=k_ali[k]) break; } if(k==n_cut) break; } } //for iteration if(i<iL_max) { i=i+simplify_step; //shift the fragment if(i>iL_max) i=iL_max; //do this to use the last missed fragment } else if(i>=iL_max) break; }//while(1) //end of one fragment }//for(i_init return score_max; } double TMscore8_search_standard( double **r1, double **r2, double **xtm, double **ytm, double **xt, int Lali, double t0[3], double u0[3][3], int simplify_step, int score_sum_method, double *Rcomm, double local_d0_search, double score_d8, double d0) { int i, m; double score_max, score, rmsd; const int kmax = Lali; int k_ali[kmax], ka, k; double t[3]; double u[3][3]; double d; //iterative parameters int n_it = 20; //maximum number of iterations int n_init_max = 6; //maximum number of different fragment length int L_ini[n_init_max]; //fragment lengths, Lali, Lali/2, Lali/4 ... 4 int L_ini_min = 4; if (Lali<L_ini_min) L_ini_min = Lali; int n_init = 0, i_init; for (i = 0; i<n_init_max - 1; i++) { n_init++; L_ini[i] = (int)(Lali / pow(2.0, (double)i)); if (L_ini[i] <= L_ini_min) { L_ini[i] = L_ini_min; break; } } if (i == n_init_max - 1) { n_init++; L_ini[i] = L_ini_min; } score_max = -1; //find the maximum score starting from local structures superposition int i_ali[kmax], n_cut; int L_frag; //fragment length int iL_max; //maximum starting postion for the fragment for (i_init = 0; i_init<n_init; i_init++) { L_frag = L_ini[i_init]; iL_max = Lali - L_frag; i = 0; while (1) { //extract the fragment starting from position i ka = 0; for (k = 0; k<L_frag; k++) { int kk = k + i; r1[k][0] = xtm[kk][0]; r1[k][1] = xtm[kk][1]; r1[k][2] = xtm[kk][2]; r2[k][0] = ytm[kk][0]; r2[k][1] = ytm[kk][1]; r2[k][2] = ytm[kk][2]; k_ali[ka] = kk; ka++; } //extract rotation matrix based on the fragment Kabsch(r1, r2, L_frag, 1, &rmsd, t, u); if (simplify_step != 1) *Rcomm = 0; do_rotation(xtm, xt, Lali, t, u); //get subsegment of this fragment d = local_d0_search - 1; n_cut = score_fun8_standard(xt, ytm, Lali, d, i_ali, &score, score_sum_method, score_d8, d0); if (score>score_max) { score_max = score; //save the rotation matrix for (k = 0; k<3; k++) { t0[k] = t[k]; u0[k][0] = u[k][0]; u0[k][1] = u[k][1]; u0[k][2] = u[k][2]; } } //try to extend the alignment iteratively d = local_d0_search + 1; for (int it = 0; it<n_it; it++) { ka = 0; for (k = 0; k<n_cut; k++) { m = i_ali[k]; r1[k][0] = xtm[m][0]; r1[k][1] = xtm[m][1]; r1[k][2] = xtm[m][2]; r2[k][0] = ytm[m][0]; r2[k][1] = ytm[m][1]; r2[k][2] = ytm[m][2]; k_ali[ka] = m; ka++; } //extract rotation matrix based on the fragment Kabsch(r1, r2, n_cut, 1, &rmsd, t, u); do_rotation(xtm, xt, Lali, t, u); n_cut = score_fun8_standard(xt, ytm, Lali, d, i_ali, &score, score_sum_method, score_d8, d0); if (score>score_max) { score_max = score; //save the rotation matrix for (k = 0; k<3; k++) { t0[k] = t[k]; u0[k][0] = u[k][0]; u0[k][1] = u[k][1]; u0[k][2] = u[k][2]; } } //check if it converges if (n_cut == ka) { for (k = 0; k<n_cut; k++) { if (i_ali[k] != k_ali[k]) break; } if (k == n_cut) break; } } //for iteration if (i<iL_max) { i = i + simplify_step; //shift the fragment if (i>iL_max) i = iL_max; //do this to use the last missed fragment } else if (i >= iL_max) break; }//while(1) //end of one fragment }//for(i_init return score_max; } //Comprehensive TMscore search engine // input: two vector sets: x, y // an alignment invmap0[] between x and y // simplify_step: 1 or 40 or other integers // score_sum_method: 0 for score over all pairs // 8 for socre over the pairs with dist<score_d8 // output: the best rotaion matrix t, u that results in highest TMscore double detailed_search(double **r1, double **r2, double **xtm, double **ytm, double **xt, double **x, double **y, int xlen, int ylen, int invmap0[], double t[3], double u[3][3], int simplify_step, int score_sum_method, double local_d0_search, double Lnorm, double score_d8, double d0) { //x is model, y is template, try to superpose onto y int i, j, k; double tmscore; double rmsd; k=0; for(i=0; i<ylen; i++) { j=invmap0[i]; if(j>=0) //aligned { xtm[k][0]=x[j][0]; xtm[k][1]=x[j][1]; xtm[k][2]=x[j][2]; ytm[k][0]=y[i][0]; ytm[k][1]=y[i][1]; ytm[k][2]=y[i][2]; k++; } } //detailed search 40-->1 tmscore = TMscore8_search(r1, r2, xtm, ytm, xt, k, t, u, simplify_step, score_sum_method, &rmsd, local_d0_search, Lnorm, score_d8, d0); return tmscore; } double detailed_search_standard( double **r1, double **r2, double **xtm, double **ytm, double **xt, double **x, double **y, int xlen, int ylen, int invmap0[], double t[3], double u[3][3], int simplify_step, int score_sum_method, double local_d0_search, const bool& bNormalize, double Lnorm, double score_d8, double d0) { //x is model, y is template, try to superpose onto y int i, j, k; double tmscore; double rmsd; k=0; for(i=0; i<ylen; i++) { j=invmap0[i]; if(j>=0) //aligned { xtm[k][0]=x[j][0]; xtm[k][1]=x[j][1]; xtm[k][2]=x[j][2]; ytm[k][0]=y[i][0]; ytm[k][1]=y[i][1]; ytm[k][2]=y[i][2]; k++; } } //detailed search 40-->1 tmscore = TMscore8_search_standard( r1, r2, xtm, ytm, xt, k, t, u, simplify_step, score_sum_method, &rmsd, local_d0_search, score_d8, d0); if (bNormalize)// "-i", to use standard_TMscore, then bNormalize=true, else bNormalize=false; tmscore = tmscore * k / Lnorm; return tmscore; } //compute the score quickly in three iterations double get_score_fast( double **r1, double **r2, double **xtm, double **ytm, double **x, double **y, int xlen, int ylen, int invmap[], double d0, double d0_search, double t[3], double u[3][3]) { double rms, tmscore, tmscore1, tmscore2; int i, j, k; k=0; for(j=0; j<ylen; j++) { i=invmap[j]; if(i>=0) { r1[k][0]=x[i][0]; r1[k][1]=x[i][1]; r1[k][2]=x[i][2]; r2[k][0]=y[j][0]; r2[k][1]=y[j][1]; r2[k][2]=y[j][2]; xtm[k][0]=x[i][0]; xtm[k][1]=x[i][1]; xtm[k][2]=x[i][2]; ytm[k][0]=y[j][0]; ytm[k][1]=y[j][1]; ytm[k][2]=y[j][2]; k++; } else if(i!=-1) PrintErrorAndQuit("Wrong map!\n"); } Kabsch(r1, r2, k, 1, &rms, t, u); //evaluate score double di; const int len=k; double dis[len]; double d00=d0_search; double d002=d00*d00; double d02=d0*d0; int n_ali=k; double xrot[3]; tmscore=0; for(k=0; k<n_ali; k++) { transform(t, u, &xtm[k][0], xrot); di=dist(xrot, &ytm[k][0]); dis[k]=di; tmscore += 1/(1+di/d02); } //second iteration double d002t=d002; while(1) { j=0; for(k=0; k<n_ali; k++) { if(dis[k]<=d002t) { r1[j][0]=xtm[k][0]; r1[j][1]=xtm[k][1]; r1[j][2]=xtm[k][2]; r2[j][0]=ytm[k][0]; r2[j][1]=ytm[k][1]; r2[j][2]=ytm[k][2]; j++; } } //there are not enough feasible pairs, relieve the threshold if(j<3 && n_ali>3) d002t += 0.5; else break; } if(n_ali!=j) { Kabsch(r1, r2, j, 1, &rms, t, u); tmscore1=0; for(k=0; k<n_ali; k++) { transform(t, u, &xtm[k][0], xrot); di=dist(xrot, &ytm[k][0]); dis[k]=di; tmscore1 += 1/(1+di/d02); } //third iteration d002t=d002+1; while(1) { j=0; for(k=0; k<n_ali; k++) { if(dis[k]<=d002t) { r1[j][0]=xtm[k][0]; r1[j][1]=xtm[k][1]; r1[j][2]=xtm[k][2]; r2[j][0]=ytm[k][0]; r2[j][1]=ytm[k][1]; r2[j][2]=ytm[k][2]; j++; } } //there are not enough feasible pairs, relieve the threshold if(j<3 && n_ali>3) d002t += 0.5; else break; } //evaluate the score Kabsch(r1, r2, j, 1, &rms, t, u); tmscore2=0; for(k=0; k<n_ali; k++) { transform(t, u, &xtm[k][0], xrot); di=dist(xrot, &ytm[k][0]); tmscore2 += 1/(1+di/d02); } } else { tmscore1=tmscore; tmscore2=tmscore; } if(tmscore1>=tmscore) tmscore=tmscore1; if(tmscore2>=tmscore) tmscore=tmscore2; return tmscore; // no need to normalize this score because it will not be used for latter scoring } //perform gapless threading to find the best initial alignment //input: x, y, xlen, ylen //output: y2x0 stores the best alignment: e.g., //y2x0[j]=i means: //the jth element in y is aligned to the ith element in x if i>=0 //the jth element in y is aligned to a gap in x if i==-1 double get_initial(double **r1, double **r2, double **xtm, double **ytm, double **x, double **y, int xlen, int ylen, int *y2x, double d0, double d0_search, const bool fast_opt, double t[3], double u[3][3]) { int min_len=getmin(xlen, ylen); if(min_len<3) PrintErrorAndQuit("Sequence is too short <3!\n"); int min_ali= min_len/2; //minimum size of considered fragment if(min_ali<=5) min_ali=5; int n1, n2; n1 = -ylen+min_ali; n2 = xlen-min_ali; int i, j, k, k_best; double tmscore, tmscore_max=-1; k_best=n1; for(k=n1; k<=n2; k+=(fast_opt)?5:1) { //get the map for(j=0; j<ylen; j++) { i=j+k; if(i>=0 && i<xlen) y2x[j]=i; else y2x[j]=-1; } //evaluate the map quickly in three iterations //this is not real tmscore, it is used to evaluate the goodness of the initial alignment tmscore=get_score_fast(r1, r2, xtm, ytm, x, y, xlen, ylen, y2x, d0,d0_search, t, u); if(tmscore>=tmscore_max) { tmscore_max=tmscore; k_best=k; } } //extract the best map k=k_best; for(j=0; j<ylen; j++) { i=j+k; if(i>=0 && i<xlen) y2x[j]=i; else y2x[j]=-1; } return tmscore_max; } void smooth(int *sec, int len) { int i, j; //smooth single --x-- => ----- for (i=2; i<len-2; i++) { if(sec[i]==2 || sec[i]==4) { j=sec[i]; if (sec[i-2]!=j && sec[i-1]!=j && sec[i+1]!=j && sec[i+2]!=j) sec[i]=1; } } // smooth double // --xx-- => ------ for (i=0; i<len-5; i++) { //helix if (sec[i]!=2 && sec[i+1]!=2 && sec[i+2]==2 && sec[i+3]==2 && sec[i+4]!=2 && sec[i+5]!= 2) { sec[i+2]=1; sec[i+3]=1; } //beta if (sec[i]!=4 && sec[i+1]!=4 && sec[i+2]==4 && sec[i+3]==4 && sec[i+4]!=4 && sec[i+5]!= 4) { sec[i+2]=1; sec[i+3]=1; } } //smooth connect for (i=0; i<len-2; i++) { if (sec[i]==2 && sec[i+1]!=2 && sec[i+2]==2) sec[i+1]=2; else if(sec[i]==4 && sec[i+1]!=4 && sec[i+2]==4) sec[i+1]=4; } } char sec_str(double dis13, double dis14, double dis15, double dis24, double dis25, double dis35) { char s='C'; double delta=2.1; if (fabs(dis15-6.37)<delta && fabs(dis14-5.18)<delta && fabs(dis25-5.18)<delta && fabs(dis13-5.45)<delta && fabs(dis24-5.45)<delta && fabs(dis35-5.45)<delta) { s='H'; //helix return s; } delta=1.42; if (fabs(dis15-13 )<delta && fabs(dis14-10.4)<delta && fabs(dis25-10.4)<delta && fabs(dis13-6.1 )<delta && fabs(dis24-6.1 )<delta && fabs(dis35-6.1 )<delta) { s='E'; //strand return s; } if (dis15 < 8) s='T'; //turn return s; } /* secondary stucture assignment for protein: * 1->coil, 2->helix, 3->turn, 4->strand */ void make_sec(double **x, int len, char *sec) { int j1, j2, j3, j4, j5; double d13, d14, d15, d24, d25, d35; for(int i=0; i<len; i++) { sec[i]='C'; j1=i-2; j2=i-1; j3=i; j4=i+1; j5=i+2; if(j1>=0 && j5<len) { d13=sqrt(dist(x[j1], x[j3])); d14=sqrt(dist(x[j1], x[j4])); d15=sqrt(dist(x[j1], x[j5])); d24=sqrt(dist(x[j2], x[j4])); d25=sqrt(dist(x[j2], x[j5])); d35=sqrt(dist(x[j3], x[j5])); sec[i]=sec_str(d13, d14, d15, d24, d25, d35); } } sec[len]=0; } //get initial alignment from secondary structure alignment //input: x, y, xlen, ylen //output: y2x stores the best alignment: e.g., //y2x[j]=i means: //the jth element in y is aligned to the ith element in x if i>=0 //the jth element in y is aligned to a gap in x if i==-1 void get_initial_ss(bool **path, double **val, const char *secx, const char *secy, int xlen, int ylen, int *y2x) { double gap_open=-1.0; NWDP_TM(path, val, secx, secy, xlen, ylen, gap_open, y2x); } // get_initial5 in TMalign fortran, get_initial_local in TMalign c by yangji //get initial alignment of local structure superposition //input: x, y, xlen, ylen //output: y2x stores the best alignment: e.g., //y2x[j]=i means: //the jth element in y is aligned to the ith element in x if i>=0 //the jth element in y is aligned to a gap in x if i==-1 bool get_initial5( double **r1, double **r2, double **xtm, double **ytm, bool **path, double **val, double **x, double **y, int xlen, int ylen, int *y2x, double d0, double d0_search, const bool fast_opt, const double D0_MIN) { double GL, rmsd; double t[3]; double u[3][3]; double d01 = d0 + 1.5; if (d01 < D0_MIN) d01 = D0_MIN; double d02 = d01*d01; double GLmax = 0; int aL = getmin(xlen, ylen); int *invmap = new int[ylen + 1]; // jump on sequence1--------------> int n_jump1 = 0; if (xlen > 250) n_jump1 = 45; else if (xlen > 200) n_jump1 = 35; else if (xlen > 150) n_jump1 = 25; else n_jump1 = 15; if (n_jump1 > (xlen / 3)) n_jump1 = xlen / 3; // jump on sequence2--------------> int n_jump2 = 0; if (ylen > 250) n_jump2 = 45; else if (ylen > 200) n_jump2 = 35; else if (ylen > 150) n_jump2 = 25; else n_jump2 = 15; if (n_jump2 > (ylen / 3)) n_jump2 = ylen / 3; // fragment to superimpose--------------> int n_frag[2] = { 20, 100 }; if (n_frag[0] > (aL / 3)) n_frag[0] = aL / 3; if (n_frag[1] > (aL / 2)) n_frag[1] = aL / 2; // start superimpose search--------------> if (fast_opt) { n_jump1*=5; n_jump2*=5; } bool flag = false; for (int i_frag = 0; i_frag < 2; i_frag++) { int m1 = xlen - n_frag[i_frag] + 1; int m2 = ylen - n_frag[i_frag] + 1; for (int i = 0; i<m1; i = i + n_jump1) //index starts from 0, different from FORTRAN { for (int j = 0; j<m2; j = j + n_jump2) { for (int k = 0; k<n_frag[i_frag]; k++) //fragment in y { r1[k][0] = x[k + i][0]; r1[k][1] = x[k + i][1]; r1[k][2] = x[k + i][2]; r2[k][0] = y[k + j][0]; r2[k][1] = y[k + j][1]; r2[k][2] = y[k + j][2]; } // superpose the two structures and rotate it Kabsch(r1, r2, n_frag[i_frag], 1, &rmsd, t, u); double gap_open = 0.0; NWDP_TM(path, val, x, y, xlen, ylen, t, u, d02, gap_open, invmap); GL = get_score_fast(r1, r2, xtm, ytm, x, y, xlen, ylen, invmap, d0, d0_search, t, u); if (GL>GLmax) { GLmax = GL; for (int ii = 0; ii<ylen; ii++) y2x[ii] = invmap[ii]; flag = true; } } } } delete[] invmap; return flag; } void score_matrix_rmsd_sec( double **r1, double **r2, double **score, const char *secx, const char *secy, double **x, double **y, int xlen, int ylen, int *y2x, const double D0_MIN, double d0) { double t[3], u[3][3]; double rmsd, dij; double d01=d0+1.5; if(d01 < D0_MIN) d01=D0_MIN; double d02=d01*d01; double xx[3]; int i, k=0; for(int j=0; j<ylen; j++) { i=y2x[j]; if(i>=0) { r1[k][0]=x[i][0]; r1[k][1]=x[i][1]; r1[k][2]=x[i][2]; r2[k][0]=y[j][0]; r2[k][1]=y[j][1]; r2[k][2]=y[j][2]; k++; } } Kabsch(r1, r2, k, 1, &rmsd, t, u); for(int ii=0; ii<xlen; ii++) { transform(t, u, &x[ii][0], xx); for(int jj=0; jj<ylen; jj++) { dij=dist(xx, &y[jj][0]); if (secx[ii]==secy[jj]) score[ii+1][jj+1] = 1.0/(1+dij/d02) + 0.5; else score[ii+1][jj+1] = 1.0/(1+dij/d02); } } } //get initial alignment from secondary structure and previous alignments //input: x, y, xlen, ylen //output: y2x stores the best alignment: e.g., //y2x[j]=i means: //the jth element in y is aligned to the ith element in x if i>=0 //the jth element in y is aligned to a gap in x if i==-1 void get_initial_ssplus(double **r1, double **r2, double **score, bool **path, double **val, const char *secx, const char *secy, double **x, double **y, int xlen, int ylen, int *y2x0, int *y2x, const double D0_MIN, double d0) { //create score matrix for DP score_matrix_rmsd_sec(r1, r2, score, secx, secy, x, y, xlen, ylen, y2x0, D0_MIN,d0); double gap_open=-1.0; NWDP_TM(score, path, val, xlen, ylen, gap_open, y2x); } void find_max_frag(double **x, int len, int *start_max, int *end_max, double dcu0, const bool fast_opt) { int r_min, fra_min=4; //minimum fragment for search if (fast_opt) fra_min=8; int start; int Lfr_max=0; r_min= (int) (len*1.0/3.0); //minimum fragment, in case too small protein if(r_min > fra_min) r_min=fra_min; int inc=0; double dcu0_cut=dcu0*dcu0;; double dcu_cut=dcu0_cut; while(Lfr_max < r_min) { Lfr_max=0; int j=1; //number of residues at nf-fragment start=0; for(int i=1; i<len; i++) { if(dist(x[i-1], x[i]) < dcu_cut) { j++; if(i==(len-1)) { if(j > Lfr_max) { Lfr_max=j; *start_max=start; *end_max=i; } j=1; } } else { if(j>Lfr_max) { Lfr_max=j; *start_max=start; *end_max=i-1; } j=1; start=i; } }// for i; if(Lfr_max < r_min) { inc++; double dinc=pow(1.1, (double) inc) * dcu0; dcu_cut= dinc*dinc; } }//while <; } //perform fragment gapless threading to find the best initial alignment //input: x, y, xlen, ylen //output: y2x0 stores the best alignment: e.g., //y2x0[j]=i means: //the jth element in y is aligned to the ith element in x if i>=0 //the jth element in y is aligned to a gap in x if i==-1 double get_initial_fgt(double **r1, double **r2, double **xtm, double **ytm, double **x, double **y, int xlen, int ylen, int *y2x, double d0, double d0_search, double dcu0, const bool fast_opt, double t[3], double u[3][3]) { int fra_min=4; //minimum fragment for search if (fast_opt) fra_min=8; int fra_min1=fra_min-1; //cutoff for shift, save time int xstart=0, ystart=0, xend=0, yend=0; find_max_frag(x, xlen, &xstart, &xend, dcu0, fast_opt); find_max_frag(y, ylen, &ystart, ¥d, dcu0, fast_opt); int Lx = xend-xstart+1; int Ly = yend-ystart+1; int *ifr, *y2x_; int L_fr=getmin(Lx, Ly); ifr= new int[L_fr]; y2x_= new int[ylen+1]; //select what piece will be used. The original implement may cause //asymetry, but only when xlen==ylen and Lx==Ly //if L1=Lfr1 and L2=Lfr2 (normal proteins), it will be the same as initial1 if(Lx<Ly || (Lx==Ly && xlen<ylen)) { for(int i=0; i<L_fr; i++) ifr[i]=xstart+i; } else if(Lx>Ly || (Lx==Ly && xlen>ylen)) { for(int i=0; i<L_fr; i++) ifr[i]=ystart+i; } else // solve asymetric for 1x5gA vs 2q7nA5 { /* In this case, L0==xlen==ylen; L_fr==Lx==Ly */ int L0=xlen; double tmscore, tmscore_max=-1; int i, j, k; int n1, n2; int min_len; int min_ali; /* part 1, normalized by xlen */ for(i=0; i<L_fr; i++) ifr[i]=xstart+i; if(L_fr==L0) { n1= (int)(L0*0.1); //my index starts from 0 n2= (int)(L0*0.89); j=0; for(i=n1; i<= n2; i++) { ifr[j]=ifr[i]; j++; } L_fr=j; } int L1=L_fr; min_len=getmin(L1, ylen); min_ali= (int) (min_len/2.5); //minimum size of considered fragment if(min_ali<=fra_min1) min_ali=fra_min1; n1 = -ylen+min_ali; n2 = L1-min_ali; for(k=n1; k<=n2; k+=(fast_opt)?3:1) { //get the map for(j=0; j<ylen; j++) { i=j+k; if(i>=0 && i<L1) y2x_[j]=ifr[i]; else y2x_[j]=-1; } //evaluate the map quickly in three iterations tmscore=get_score_fast(r1, r2, xtm, ytm, x, y, xlen, ylen, y2x_, d0, d0_search, t, u); if(tmscore>=tmscore_max) { tmscore_max=tmscore; for(j=0; j<ylen; j++) y2x[j]=y2x_[j]; } } /* part 2, normalized by ylen */ L_fr=Ly; for(i=0; i<L_fr; i++) ifr[i]=ystart+i; if (L_fr==L0) { n1= (int)(L0*0.1); //my index starts from 0 n2= (int)(L0*0.89); j=0; for(i=n1; i<= n2; i++) { ifr[j]=ifr[i]; j++; } L_fr=j; } int L2=L_fr; min_len=getmin(xlen, L2); min_ali= (int) (min_len/2.5); //minimum size of considered fragment if(min_ali<=fra_min1) min_ali=fra_min1; n1 = -L2+min_ali; n2 = xlen-min_ali; for(k=n1; k<=n2; k++) { //get the map for(j=0; j<ylen; j++) y2x_[j]=-1; for(j=0; j<L2; j++) { i=j+k; if(i>=0 && i<xlen) y2x_[ifr[j]]=i; } //evaluate the map quickly in three iterations tmscore=get_score_fast(r1, r2, xtm, ytm, x, y, xlen, ylen, y2x_, d0,d0_search, t, u); if(tmscore>=tmscore_max) { tmscore_max=tmscore; for(j=0; j<ylen; j++) y2x[j]=y2x_[j]; } } delete [] ifr; delete [] y2x_; return tmscore_max; } int L0=getmin(xlen, ylen); //non-redundant to get_initial1 if(L_fr==L0) { int n1= (int)(L0*0.1); //my index starts from 0 int n2= (int)(L0*0.89); int j=0; for(int i=n1; i<= n2; i++) { ifr[j]=ifr[i]; j++; } L_fr=j; } //gapless threading for the extracted fragment double tmscore, tmscore_max=-1; if(Lx<Ly || (Lx==Ly && xlen<=ylen)) { int L1=L_fr; int min_len=getmin(L1, ylen); int min_ali= (int) (min_len/2.5); //minimum size of considered fragment if(min_ali<=fra_min1) min_ali=fra_min1; int n1, n2; n1 = -ylen+min_ali; n2 = L1-min_ali; int i, j, k; for(k=n1; k<=n2; k+=(fast_opt)?3:1) { //get the map for(j=0; j<ylen; j++) { i=j+k; if(i>=0 && i<L1) y2x_[j]=ifr[i]; else y2x_[j]=-1; } //evaluate the map quickly in three iterations tmscore=get_score_fast(r1, r2, xtm, ytm, x, y, xlen, ylen, y2x_, d0, d0_search, t, u); if(tmscore>=tmscore_max) { tmscore_max=tmscore; for(j=0; j<ylen; j++) y2x[j]=y2x_[j]; } } } else { int L2=L_fr; int min_len=getmin(xlen, L2); int min_ali= (int) (min_len/2.5); //minimum size of considered fragment if(min_ali<=fra_min1) min_ali=fra_min1; int n1, n2; n1 = -L2+min_ali; n2 = xlen-min_ali; int i, j, k; for(k=n1; k<=n2; k++) { //get the map for(j=0; j<ylen; j++) y2x_[j]=-1; for(j=0; j<L2; j++) { i=j+k; if(i>=0 && i<xlen) y2x_[ifr[j]]=i; } //evaluate the map quickly in three iterations tmscore=get_score_fast(r1, r2, xtm, ytm, x, y, xlen, ylen, y2x_, d0,d0_search, t, u); if(tmscore>=tmscore_max) { tmscore_max=tmscore; for(j=0; j<ylen; j++) y2x[j]=y2x_[j]; } } } delete [] ifr; delete [] y2x_; return tmscore_max; } //heuristic run of dynamic programing iteratively to find the best alignment //input: initial rotation matrix t, u // vectors x and y, d0 //output: best alignment that maximizes the TMscore, will be stored in invmap double DP_iter(double **r1, double **r2, double **xtm, double **ytm, double **xt, bool **path, double **val, double **x, double **y, int xlen, int ylen, double t[3], double u[3][3], int invmap0[], int g1, int g2, int iteration_max, double local_d0_search, double D0_MIN, double Lnorm, double d0, double score_d8) { double gap_open[2]={-0.6, 0}; double rmsd; int *invmap=new int[ylen+1]; int iteration, i, j, k; double tmscore, tmscore_max, tmscore_old=0; int score_sum_method=8, simplify_step=40; tmscore_max=-1; //double d01=d0+1.5; double d02=d0*d0; for(int g=g1; g<g2; g++) { for(iteration=0; iteration<iteration_max; iteration++) { NWDP_TM(path, val, x, y, xlen, ylen, t, u, d02, gap_open[g], invmap); k=0; for(j=0; j<ylen; j++) { i=invmap[j]; if(i>=0) //aligned { xtm[k][0]=x[i][0]; xtm[k][1]=x[i][1]; xtm[k][2]=x[i][2]; ytm[k][0]=y[j][0]; ytm[k][1]=y[j][1]; ytm[k][2]=y[j][2]; k++; } } tmscore = TMscore8_search(r1, r2, xtm, ytm, xt, k, t, u, simplify_step, score_sum_method, &rmsd, local_d0_search, Lnorm, score_d8, d0); if(tmscore>tmscore_max) { tmscore_max=tmscore; for(i=0; i<ylen; i++) invmap0[i]=invmap[i]; } if(iteration>0) { if(fabs(tmscore_old-tmscore)<0.000001) break; } tmscore_old=tmscore; }// for iteration }//for gapopen delete []invmap; return tmscore_max; } void output_superpose(const string xname, const string yname, const string fname_super, double t[3], double u[3][3], const int ter_opt, const int mirror_opt, const char *seqM, const char *seqxA, const char *seqyA, const vector<string>&resi_vec1, const vector<string>&resi_vec2, const char *chainID1, const char *chainID2, const int xlen, const int ylen, const double d0A, const int n_ali8, const double rmsd, const double TM1, const double Liden) { stringstream buf; stringstream buf_all; stringstream buf_atm; stringstream buf_all_atm; stringstream buf_all_atm_lig; stringstream buf_pdb; stringstream buf_pymol; stringstream buf_tm; string line; double x[3]; // before transform double x1[3]; // after transform bool after_ter; // true if passed the "TER" line in PDB string asym_id; // chain ID buf_tm<<"REMARK TM-align" <<"\nREMARK Chain 1:"<<setw(11)<<left<<xname+chainID1<<" Size= "<<xlen <<"\nREMARK Chain 2:"<<setw(11)<<yname+chainID2<<right<<" Size= "<<ylen <<" (TM-score is normalized by "<<setw(4)<<ylen<<", d0=" <<setiosflags(ios::fixed)<<setprecision(2)<<setw(6)<<d0A<<")" <<"\nREMARK Aligned length="<<setw(4)<<n_ali8<<", RMSD=" <<setw(6)<<setiosflags(ios::fixed)<<setprecision(2)<<rmsd <<", TM-score="<<setw(7)<<setiosflags(ios::fixed)<<setprecision(5)<<TM1 <<", ID="<<setw(5)<<setiosflags(ios::fixed)<<setprecision(3) <<((n_ali8>0)?Liden/n_ali8:0)<<endl; string rasmol_CA_header="load inline\nselect *A\nwireframe .45\nselect *B\nwireframe .20\nselect all\ncolor white\n"; string rasmol_cartoon_header="load inline\nselect all\ncartoon\nselect *A\ncolor blue\nselect *B\ncolor red\nselect ligand\nwireframe 0.25\nselect solvent\nspacefill 0.25\nselect all\nexit\n"+buf_tm.str(); buf<<rasmol_CA_header; buf_all<<rasmol_CA_header; buf_atm<<rasmol_cartoon_header; buf_all_atm<<rasmol_cartoon_header; buf_all_atm_lig<<rasmol_cartoon_header; /* for PDBx/mmCIF only */ map<string,int> _atom_site; int atom_site_pos; vector<string> line_vec; string atom; // 4-character atom name string AA; // 3-character residue name string resi; // 4-character residue sequence number string inscode; // 1-character insertion code string model_index; // model index bool is_mmcif=false; int chain_num=0; /* used for CONECT record of chain1 */ int ca_idx1=0; // all CA atoms int lig_idx1=0; // all atoms vector <int> idx_vec; /* used for CONECT record of chain2 */ int ca_idx2=0; // all CA atoms int lig_idx2=0; // all atoms /* extract aligned region */ vector<string> resi_aln1; vector<string> resi_aln2; int i1=-1; int i2=-1; int i; for (i=0;i<strlen(seqM);i++) { i1+=(seqxA[i]!='-'); i2+=(seqyA[i]!='-'); if (seqM[i]==' ') continue; resi_aln1.push_back(resi_vec1[i1].substr(0,4)); resi_aln2.push_back(resi_vec2[i2].substr(0,4)); if (seqM[i]!=':') continue; buf <<"select "<<resi_aln1.back()<<":A," <<resi_aln2.back()<<":B\ncolor red\n"; buf_all<<"select "<<resi_aln1.back()<<":A," <<resi_aln2.back()<<":B\ncolor red\n"; } buf<<"select all\nexit\n"<<buf_tm.str(); buf_all<<"select all\nexit\n"<<buf_tm.str(); ifstream fin; /* read first file */ after_ter=false; asym_id=""; fin.open(xname.c_str()); while (fin.good()) { getline(fin, line); if (ter_opt>=3 && line.compare(0,3,"TER")==0) after_ter=true; if (is_mmcif==false && line.size()>=54 && (line.compare(0, 6, "ATOM ")==0 || line.compare(0, 6, "HETATM")==0)) // PDB format { x[0]=atof(line.substr(30,8).c_str()); x[1]=atof(line.substr(38,8).c_str()); x[2]=atof(line.substr(46,8).c_str()); if (mirror_opt) x[2]=-x[2]; transform(t, u, x, x1); buf_pdb<<line.substr(0,30)<<setiosflags(ios::fixed) <<setprecision(3) <<setw(8)<<x1[0] <<setw(8)<<x1[1] <<setw(8)<<x1[2] <<line.substr(54)<<'\n'; if (line[16]!='A' && line[16]!=' ') continue; if (after_ter && line.compare(0,6,"ATOM ")==0) continue; lig_idx1++; buf_all_atm_lig<<line.substr(0,6)<<setw(5)<<lig_idx1 <<line.substr(11,9)<<" A"<<line.substr(22,8) <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0]<<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; if (after_ter || line.compare(0,6,"ATOM ")) continue; if (ter_opt>=2) { if (ca_idx1 && asym_id.size() && asym_id!=line.substr(21,1)) { after_ter=true; continue; } asym_id=line[21]; } buf_all_atm<<"ATOM "<<setw(5)<<lig_idx1 <<line.substr(11,9)<<" A"<<line.substr(22,8) <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0]<<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; if (find(resi_aln1.begin(),resi_aln1.end(),line.substr(22,4) )!=resi_aln1.end()) { buf_atm<<"ATOM "<<setw(5)<<lig_idx1 <<line.substr(11,9)<<" A"<<line.substr(22,8) <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0]<<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; } if (line.substr(12,4)!=" CA ") continue; ca_idx1++; buf_all<<"ATOM "<<setw(5)<<ca_idx1 <<" CA "<<line.substr(17,3)<<" A"<<line.substr(22,8) <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0]<<setw(8)<<x1[1]<<setw(8)<<x1[2]<<'\n'; if (find(resi_aln1.begin(),resi_aln1.end(),line.substr(22,4) )==resi_aln1.end()) continue; buf<<"ATOM "<<setw(5)<<ca_idx1 <<" CA "<<line.substr(17,3)<<" A"<<line.substr(22,8) <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0]<<setw(8)<<x1[1]<<setw(8)<<x1[2]<<'\n'; idx_vec.push_back(ca_idx1); } else if (line.compare(0,5,"loop_")==0) // PDBx/mmCIF { while(1) { if (fin.good()) getline(fin, line); else PrintErrorAndQuit("ERROR! Unexpected end of "+xname); if (line.size()) break; } if (line.compare(0,11,"_atom_site.")) continue; _atom_site.clear(); atom_site_pos=0; _atom_site[line.substr(11,line.size()-12)]=atom_site_pos; while(1) { if (fin.good()) getline(fin, line); else PrintErrorAndQuit("ERROR! Unexpected end of "+xname); if (line.size()==0) continue; if (line.compare(0,11,"_atom_site.")) break; _atom_site[line.substr(11,line.size()-12)]=++atom_site_pos; } if (is_mmcif==false) { buf_pdb.str(string()); is_mmcif=true; } while(1) { line_vec.clear(); split(line,line_vec); if (line_vec[_atom_site["group_PDB"]]!="ATOM" && line_vec[_atom_site["group_PDB"]]!="HETATM") break; if (_atom_site.count("pdbx_PDB_model_num")) { if (model_index.size() && model_index!= line_vec[_atom_site["pdbx_PDB_model_num"]]) break; model_index=line_vec[_atom_site["pdbx_PDB_model_num"]]; } x[0]=atof(line_vec[_atom_site["Cartn_x"]].c_str()); x[1]=atof(line_vec[_atom_site["Cartn_y"]].c_str()); x[2]=atof(line_vec[_atom_site["Cartn_z"]].c_str()); if (mirror_opt) x[2]=-x[2]; transform(t, u, x, x1); if (_atom_site.count("label_alt_id")==0 || line_vec[_atom_site["label_alt_id"]]=="." || line_vec[_atom_site["label_alt_id"]]=="A") { atom=line_vec[_atom_site["label_atom_id"]]; if (atom[0]=='"') atom=atom.substr(1); if (atom.size() && atom[atom.size()-1]=='"') atom=atom.substr(0,atom.size()-1); if (atom.size()==0) atom=" "; else if (atom.size()==1) atom=" "+atom+" "; else if (atom.size()==2) atom=" "+atom+" "; else if (atom.size()==3) atom=" "+atom; else if (atom.size()>=5) atom=atom.substr(0,4); AA=line_vec[_atom_site["label_comp_id"]]; // residue name if (AA.size()==1) AA=" "+AA; else if (AA.size()==2) AA=" " +AA; else if (AA.size()>=4) AA=AA.substr(0,3); if (_atom_site.count("auth_seq_id")) resi=line_vec[_atom_site["auth_seq_id"]]; else resi=line_vec[_atom_site["label_seq_id"]]; while (resi.size()<4) resi=' '+resi; if (resi.size()>4) resi=resi.substr(0,4); inscode=' '; if (_atom_site.count("pdbx_PDB_ins_code") && line_vec[_atom_site["pdbx_PDB_ins_code"]]!="?") inscode=line_vec[_atom_site["pdbx_PDB_ins_code"]][0]; if (_atom_site.count("auth_asym_id")) { if (ter_opt>=2 && ca_idx1 && asym_id.size() && asym_id!=line_vec[_atom_site["auth_asym_id"]]) after_ter=true; asym_id=line_vec[_atom_site["auth_asym_id"]]; } else if (_atom_site.count("label_asym_id")) { if (ter_opt>=2 && ca_idx1 && asym_id.size() && asym_id!=line_vec[_atom_site["label_asym_id"]]) after_ter=true; asym_id=line_vec[_atom_site["label_asym_id"]]; } buf_pdb<<left<<setw(6) <<line_vec[_atom_site["group_PDB"]]<<right <<setw(5)<<lig_idx1%100000<<' '<<atom<<' ' <<AA<<" "<<asym_id[asym_id.size()-1] <<resi<<inscode<<" " <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0] <<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; if (after_ter==false || line_vec[_atom_site["group_pdb"]]=="HETATM") { lig_idx1++; buf_all_atm_lig<<left<<setw(6) <<line_vec[_atom_site["group_PDB"]]<<right <<setw(5)<<lig_idx1%100000<<' '<<atom<<' ' <<AA<<" A"<<resi<<inscode<<" " <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0] <<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; if (after_ter==false && line_vec[_atom_site["group_PDB"]]=="ATOM") { buf_all_atm<<"ATOM "<<setw(6) <<setw(5)<<lig_idx1%100000<<' '<<atom<<' ' <<AA<<" A"<<resi<<inscode<<" " <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0] <<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; if (find(resi_aln1.begin(),resi_aln1.end(),resi )!=resi_aln1.end()) { buf_atm<<"ATOM "<<setw(6) <<setw(5)<<lig_idx1%100000<<' ' <<atom<<' '<<AA<<" A"<<resi<<inscode<<" " <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0] <<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; } if (atom==" CA ") { ca_idx1++; buf_all<<"ATOM "<<setw(6) <<setw(5)<<ca_idx1%100000<<" CA " <<AA<<" A"<<resi<<inscode<<" " <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0] <<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; if (find(resi_aln1.begin(),resi_aln1.end(),resi )!=resi_aln1.end()) { buf<<"ATOM "<<setw(6) <<setw(5)<<ca_idx1%100000<<" CA " <<AA<<" A"<<resi<<inscode<<" " <<setiosflags(ios::fixed)<<setprecision(3) <<setw(8)<<x1[0] <<setw(8)<<x1[1] <<setw(8)<<x1[2]<<'\n'; idx_vec.push_back(ca_idx1); } } } } } while(1) { if (fin.good()) getline(fin, line); else break; if (line.size()) break; } } } else if (line.size() && is_mmcif==false) { buf_pdb<<line<<'\n'; if (ter_opt>=1 && line.compare(0,3,"END")==0) break; } } fin.close(); buf<<"TER\n"; buf_all<<"TER\n"; buf_atm<<"TER\n"; buf_all_atm<<"TER\n"; buf_all_atm_lig<<"TER\n"; for (i=1;i<ca_idx1;i++) buf_all<<"CONECT" <<setw(5)<<i%100000<<setw(5)<<(i+1)%100000<<'\n'; for (i=1;i<idx_vec.size();i++) buf<<"CONECT" <<setw(5)<<idx_vec[i-1]%100000<<setw(5)<<idx_vec[i]%100000<<'\n'; idx_vec.clear(); /* read second file */ after_ter=false; asym_id=""; fin.open(yname.c_str()); while (fin.good()) { getline(fin, line); if (ter_opt>=3 && line.compare(0,3,"TER")==0) after_ter=true; if (line.size()>=54 && (line.compare(0, 6, "ATOM ")==0 || line.compare(0, 6, "HETATM")==0)) // PDB format { if (line[16]!='A' && line[16]!=' ') continue; if (after_ter && line.compare(0,6,"ATOM ")==0) continue; lig_idx2++; buf_all_atm_lig<<line.substr(0,6)<<setw(5)<<lig_idx1+lig_idx2 <<line.substr(11,9)<<" B"<<line.substr(22,32)<<'\n'; if (after_ter || line.compare(0,6,"ATOM ")) continue; if (ter_opt>=2) { if (ca_idx2 && asym_id.size() && asym_id!=line.substr(21,1)) { after_ter=true; continue; } asym_id=line[21]; } buf_all_atm<<"ATOM "<<setw(5)<<lig_idx1+lig_idx2 <<line.substr(11,9)<<" B"<<line.substr(22,32)<<'\n'; if (find(resi_aln2.begin(),resi_aln2.end(),line.substr(22,4) )!=resi_aln2.end()) { buf_atm<<"ATOM "<<setw(5)<<lig_idx1+lig_idx2 <<line.substr(11,9)<<" B"<<line.substr(22,32)<<'\n'; } if (line.substr(12,4)!=" CA ") continue; ca_idx2++; buf_all<<"ATOM "<<setw(5)<<ca_idx1+ca_idx2<<" CA " <<line.substr(17,3)<<" B"<<line.substr(22,32)<<'\n'; if (find(resi_aln2.begin(),resi_aln2.end(),line.substr(22,4) )==resi_aln2.end()) continue; buf<<"ATOM "<<setw(5)<<ca_idx1+ca_idx2<<" CA " <<line.substr(17,3)<<" B"<<line.substr(22,32)<<'\n'; idx_vec.push_back(ca_idx1+ca_idx2); } else if (line.compare(0,5,"loop_")==0) // PDBx/mmCIF { while(1) { if (fin.good()) getline(fin, line); else PrintErrorAndQuit("ERROR! Unexpected end of "+yname); if (line.size()) break; } if (line.compare(0,11,"_atom_site.")) continue; _atom_site.clear(); atom_site_pos=0; _atom_site[line.substr(11,line.size()-12)]=atom_site_pos; while(1) { if (fin.good()) getline(fin, line); else PrintErrorAndQuit("ERROR! Unexpected end of "+yname); if (line.size()==0) continue; if (line.compare(0,11,"_atom_site.")) break; _atom_site[line.substr(11,line.size()-12)]=++atom_site_pos; } while(1) { line_vec.clear(); split(line,line_vec); if (line_vec[_atom_site["group_PDB"]]!="ATOM" && line_vec[_atom_site["group_PDB"]]!="HETATM") break; if (_atom_site.count("pdbx_PDB_model_num")) { if (model_index.size() && model_index!= line_vec[_atom_site["pdbx_PDB_model_num"]]) break; model_index=line_vec[_atom_site["pdbx_PDB_model_num"]]; } if (_atom_site.count("label_alt_id")==0 || line_vec[_atom_site["label_alt_id"]]=="." || line_vec[_atom_site["label_alt_id"]]=="A") { atom=line_vec[_atom_site["label_atom_id"]]; if (atom[0]=='"') atom=atom.substr(1); if (atom.size() && atom[atom.size()-1]=='"') atom=atom.substr(0,atom.size()-1); if (atom.size()==0) atom=" "; else if (atom.size()==1) atom=" "+atom+" "; else if (atom.size()==2) atom=" "+atom+" "; else if (atom.size()==3) atom=" "+atom; else if (atom.size()>=5) atom=atom.substr(0,4); AA=line_vec[_atom_site["label_comp_id"]]; // residue name if (AA.size()==1) AA=" "+AA; else if (AA.size()==2) AA=" " +AA; else if (AA.size()>=4) AA=AA.substr(0,3); if (_atom_site.count("auth_seq_id")) resi=line_vec[_atom_site["auth_seq_id"]]; else resi=line_vec[_atom_site["label_seq_id"]]; while (resi.size()<4) resi=' '+resi; if (resi.size()>4) resi=resi.substr(0,4); inscode=' '; if (_atom_site.count("pdbx_PDB_ins_code") && line_vec[_atom_site["pdbx_PDB_ins_code"]]!="?") inscode=line_vec[_atom_site["pdbx_PDB_ins_code"]][0]; if (ter_opt>=2) { if (_atom_site.count("auth_asym_id")) { if (ca_idx2 && asym_id.size() && asym_id!=line_vec[_atom_site["auth_asym_id"]]) after_ter=true; else asym_id=line_vec[_atom_site["auth_asym_id"]]; } else if (_atom_site.count("label_asym_id")) { if (ca_idx2 && asym_id.size() && asym_id!=line_vec[_atom_site["label_asym_id"]]) after_ter=true; else asym_id=line_vec[_atom_site["label_asym_id"]]; } } if (after_ter==false || line_vec[_atom_site["group_PDB"]]=="HETATM") { lig_idx2++; buf_all_atm_lig<<left<<setw(6) <<line_vec[_atom_site["group_PDB"]]<<right <<setw(5)<<(lig_idx1+lig_idx2)%100000<<' ' <<atom<<' '<<AA<<" B"<<resi<<inscode<<" " <<setw(8)<<line_vec[_atom_site["Cartn_x"]] <<setw(8)<<line_vec[_atom_site["Cartn_y"]] <<setw(8)<<line_vec[_atom_site["Cartn_z"]] <<'\n'; if (after_ter==false && line_vec[_atom_site["group_PDB"]]=="ATOM") { buf_all_atm<<"ATOM "<<setw(6) <<setw(5)<<(lig_idx1+lig_idx2)%100000<<' ' <<atom<<' '<<AA<<" B"<<resi<<inscode<<" " <<setw(8)<<line_vec[_atom_site["Cartn_x"]] <<setw(8)<<line_vec[_atom_site["Cartn_y"]] <<setw(8)<<line_vec[_atom_site["Cartn_z"]] <<'\n'; if (find(resi_aln2.begin(),resi_aln2.end(),resi )!=resi_aln2.end()) { buf_atm<<"ATOM "<<setw(6) <<setw(5)<<(lig_idx1+lig_idx2)%100000<<' ' <<atom<<' '<<AA<<" B"<<resi<<inscode<<" " <<setw(8)<<line_vec[_atom_site["Cartn_x"]] <<setw(8)<<line_vec[_atom_site["Cartn_y"]] <<setw(8)<<line_vec[_atom_site["Cartn_z"]] <<'\n'; } if (atom==" CA ") { ca_idx2++; buf_all<<"ATOM "<<setw(6) <<setw(5)<<(ca_idx1+ca_idx2)%100000 <<" CA "<<AA<<" B"<<resi<<inscode<<" " <<setw(8)<<line_vec[_atom_site["Cartn_x"]] <<setw(8)<<line_vec[_atom_site["Cartn_y"]] <<setw(8)<<line_vec[_atom_site["Cartn_z"]] <<'\n'; if (find(resi_aln2.begin(),resi_aln2.end(),resi )!=resi_aln2.end()) { buf<<"ATOM "<<setw(6) <<setw(5)<<(ca_idx1+ca_idx2)%100000 <<" CA "<<AA<<" B"<<resi<<inscode<<" " <<setw(8)<<line_vec[_atom_site["Cartn_x"]] <<setw(8)<<line_vec[_atom_site["Cartn_y"]] <<setw(8)<<line_vec[_atom_site["Cartn_z"]] <<'\n'; idx_vec.push_back(ca_idx1+ca_idx2); } } } } } if (fin.good()) getline(fin, line); else break; } } else if (line.size()) { if (ter_opt>=1 && line.compare(0,3,"END")==0) break; } } fin.close(); buf<<"TER\n"; buf_all<<"TER\n"; buf_atm<<"TER\n"; buf_all_atm<<"TER\n"; buf_all_atm_lig<<"TER\n"; for (i=ca_idx1+1;i<ca_idx1+ca_idx2;i++) buf_all<<"CONECT" <<setw(5)<<i%100000<<setw(5)<<(i+1)%100000<<'\n'; for (i=1;i<idx_vec.size();i++) buf<<"CONECT" <<setw(5)<<idx_vec[i-1]%100000<<setw(5)<<idx_vec[i]%100000<<'\n'; idx_vec.clear(); /* write pymol script */ ofstream fp; vector<string> pml_list; pml_list.push_back(fname_super+""); pml_list.push_back(fname_super+"_atm"); pml_list.push_back(fname_super+"_all"); pml_list.push_back(fname_super+"_all_atm"); pml_list.push_back(fname_super+"_all_atm_lig"); for (i=0;i<pml_list.size();i++) { buf_pymol<<"#!/usr/bin/env pymol\n" <<"load "<<pml_list[i]<<"\n" <<"hide all\n" <<((i==0 || i==2)?("show stick\n"):("show cartoon\n")) <<"color blue, chain A\n" <<"color red, chain B\n" <<"set ray_shadow, 0\n" <<"set stick_radius, 0.3\n" <<"set sphere_scale, 0.25\n" <<"show stick, not polymer\n" <<"show sphere, not polymer\n" <<"bg_color white\n" <<"set transparency=0.2\n" <<"zoom polymer\n" <<endl; fp.open((pml_list[i]+".pml").c_str()); fp<<buf_pymol.str(); fp.close(); buf_pymol.str(string()); pml_list[i].clear(); } pml_list.clear(); /* write rasmol script */ fp.open((fname_super).c_str()); fp<<buf.str(); fp.close(); fp.open((fname_super+"_all").c_str()); fp<<buf_all.str(); fp.close(); fp.open((fname_super+"_atm").c_str()); fp<<buf_atm.str(); fp.close(); fp.open((fname_super+"_all_atm").c_str()); fp<<buf_all_atm.str(); fp.close(); fp.open((fname_super+"_all_atm_lig").c_str()); fp<<buf_all_atm_lig.str(); fp.close(); fp.open((fname_super+".pdb").c_str()); fp<<buf_pdb.str(); fp.close(); /* clear stream */ buf.str(string()); buf_all.str(string()); buf_atm.str(string()); buf_all_atm.str(string()); buf_all_atm_lig.str(string()); buf_pdb.str(string()); buf_tm.str(string()); resi_aln1.clear(); resi_aln2.clear(); asym_id.clear(); line_vec.clear(); atom.clear(); AA.clear(); resi.clear(); inscode.clear(); model_index.clear(); } /* extract rotation matrix based on TMscore8 */ void output_rotation_matrix(const char* fname_matrix, const double t[3], const double u[3][3]) { fstream fout; fout.open(fname_matrix, ios::out | ios::trunc); if (fout)// succeed { fout << "------ The rotation matrix to rotate Chain_1 to Chain_2 ------\n"; char dest[1000]; sprintf(dest, "m %18s %14s %14s %14s\n", "t[m]", "u[m][0]", "u[m][1]", "u[m][2]"); fout << string(dest); for (int k = 0; k < 3; k++) { sprintf(dest, "%d %18.10f %14.10f %14.10f %14.10f\n", k, t[k], u[k][0], u[k][1], u[k][2]); fout << string(dest); } fout << "\nCode for rotating Structure A from (x,y,z) to (X,Y,Z):\n" "for(i=0; i<L; i++)\n" "{\n" " X[i] = t[0] + u[0][0]*x[i] + u[0][1]*y[i] + u[0][2]*z[i];\n" " Y[i] = t[1] + u[1][0]*x[i] + u[1][1]*y[i] + u[1][2]*z[i];\n" " Z[i] = t[2] + u[2][0]*x[i] + u[2][1]*y[i] + u[2][2]*z[i];\n" "}\n"; fout.close(); } else cout << "Open file to output rotation matrix fail.\n"; } //output the final results void output_results( const string xname, const string yname, const char *chainID1, const char *chainID2, const int xlen, const int ylen, double t[3], double u[3][3], const double TM1, const double TM2, const double TM3, const double TM4, const double TM5, const double rmsd, const double d0_out, const char *seqM, const char *seqxA, const char *seqyA, const double Liden, const int n_ali8, const int L_ali, const double TM_ali, const double rmsd_ali, const double TM_0, const double d0_0, const double d0A, const double d0B, const double Lnorm_ass, const double d0_scale, const double d0a, const double d0u, const char* fname_matrix, const int outfmt_opt, const int ter_opt, const string fname_super, const int i_opt, const int a_opt, const bool u_opt, const bool d_opt, const int mirror_opt, const vector<string>&resi_vec1, const vector<string>&resi_vec2) { if (outfmt_opt<=0) { printf("\nName of Chain_1: %s%s (to be superimposed onto Chain_2)\n", xname.c_str(), chainID1); printf("Name of Chain_2: %s%s\n", yname.c_str(), chainID2); printf("Length of Chain_1: %d residues\n", xlen); printf("Length of Chain_2: %d residues\n\n", ylen); if (i_opt) printf("User-specified initial alignment: TM/Lali/rmsd = %7.5lf, %4d, %6.3lf\n", TM_ali, L_ali, rmsd_ali); printf("Aligned length= %d, RMSD= %6.2f, Seq_ID=n_identical/n_aligned= %4.3f\n", n_ali8, rmsd, (n_ali8>0)?Liden/n_ali8:0); printf("TM-score= %6.5f (if normalized by length of Chain_1, i.e., LN=%d, d0=%.2f)\n", TM2, xlen, d0B); printf("TM-score= %6.5f (if normalized by length of Chain_2, i.e., LN=%d, d0=%.2f)\n", TM1, ylen, d0A); if (a_opt==1) printf("TM-score= %6.5f (if normalized by average length of two structures, i.e., LN= %.1f, d0= %.2f)\n", TM3, (xlen+ylen)*0.5, d0a); if (u_opt) printf("TM-score= %6.5f (if normalized by user-specified LN=%.2f and d0=%.2f)\n", TM4, Lnorm_ass, d0u); if (d_opt) printf("TM-score= %6.5f (if scaled by user-specified d0= %.2f, and LN= %d)\n", TM5, d0_scale, ylen); printf("(You should use TM-score normalized by length of the reference structure)\n"); //output alignment printf("\n(\":\" denotes residue pairs of d < %4.1f Angstrom, ", d0_out); printf("\".\" denotes other aligned residues)\n"); printf("%s\n", seqxA); printf("%s\n", seqM); printf("%s\n", seqyA); } else if (outfmt_opt==1) { printf(">%s%s\tL=%d\td0=%.2f\tseqID=%.3f\tTM-score=%.5f\n", xname.c_str(), chainID1, xlen, d0B, Liden/xlen, TM2); printf("%s\n", seqxA); printf(">%s%s\tL=%d\td0=%.2f\tseqID=%.3f\tTM-score=%.5f\n", yname.c_str(), chainID2, ylen, d0A, Liden/ylen, TM1); printf("%s\n", seqyA); printf("# Lali=%d\tRMSD=%.2f\tseqID_ali=%.3f\n", n_ali8, rmsd, (n_ali8>0)?Liden/n_ali8:0); if (i_opt) printf("# User-specified initial alignment: TM=%.5lf\tLali=%4d\trmsd=%.3lf\n", TM_ali, L_ali, rmsd_ali); if(a_opt) printf("# TM-score=%.5f (normalized by average length of two structures: L=%.1f\td0=%.2f)\n", TM3, (xlen+ylen)*0.5, d0a); if(u_opt) printf("# TM-score=%.5f (normalized by user-specified L=%.2f\td0=%.2f)\n", TM4, Lnorm_ass, d0u); if(d_opt) printf("# TM-score=%.5f (scaled by user-specified d0=%.2f\tL=%d)\n", TM5, d0_scale, ylen); printf("$$$$\n"); } else if (outfmt_opt==2) { printf("%s%s\t%s%s\t%.4f\t%.4f\t%.2f\t%4.3f\t%4.3f\t%4.3f\t%d\t%d\t%d", xname.c_str(), chainID1, yname.c_str(), chainID2, TM2, TM1, rmsd, Liden/xlen, Liden/ylen, (n_ali8>0)?Liden/n_ali8:0, xlen, ylen, n_ali8); } cout << endl; if (strlen(fname_matrix)) output_rotation_matrix(fname_matrix, t, u); if (fname_super.size()) output_superpose(xname, yname, fname_super, t, u, ter_opt, mirror_opt, seqM, seqxA, seqyA, resi_vec1, resi_vec2, chainID1, chainID2, xlen, ylen, d0A, n_ali8, rmsd, TM1, Liden); } double standard_TMscore(double **r1, double **r2, double **xtm, double **ytm, double **xt, double **x, double **y, int xlen, int ylen, int invmap[], int& L_ali, double& RMSD, double D0_MIN, double Lnorm, double d0, double d0_search, double score_d8, double t[3], double u[3][3], const int mol_type) { D0_MIN = 0.5; Lnorm = ylen; if (mol_type>0) // RNA { if (Lnorm<=11) d0=0.3; else if(Lnorm>11 && Lnorm<=15) d0=0.4; else if(Lnorm>15 && Lnorm<=19) d0=0.5; else if(Lnorm>19 && Lnorm<=23) d0=0.6; else if(Lnorm>23 && Lnorm<30) d0=0.7; else d0=(0.6*pow((Lnorm*1.0-0.5), 1.0/2)-2.5); } else { if (Lnorm > 21) d0=(1.24*pow((Lnorm*1.0-15), 1.0/3) -1.8); else d0 = D0_MIN; if (d0 < D0_MIN) d0 = D0_MIN; } double d0_input = d0;// Scaled by seq_min double tmscore;// collected alined residues from invmap int n_al = 0; int i; for (int j = 0; j<ylen; j++) { i = invmap[j]; if (i >= 0) { xtm[n_al][0] = x[i][0]; xtm[n_al][1] = x[i][1]; xtm[n_al][2] = x[i][2]; ytm[n_al][0] = y[j][0]; ytm[n_al][1] = y[j][1]; ytm[n_al][2] = y[j][2]; r1[n_al][0] = x[i][0]; r1[n_al][1] = x[i][1]; r1[n_al][2] = x[i][2]; r2[n_al][0] = y[j][0]; r2[n_al][1] = y[j][1]; r2[n_al][2] = y[j][2]; n_al++; } else if (i != -1) PrintErrorAndQuit("Wrong map!\n"); } L_ali = n_al; Kabsch(r1, r2, n_al, 0, &RMSD, t, u); RMSD = sqrt( RMSD/(1.0*n_al) ); int temp_simplify_step = 1; int temp_score_sum_method = 0; d0_search = d0_input; double rms = 0.0; tmscore = TMscore8_search_standard(r1, r2, xtm, ytm, xt, n_al, t, u, temp_simplify_step, temp_score_sum_method, &rms, d0_input, score_d8, d0); tmscore = tmscore * n_al / (1.0*Lnorm); return tmscore; } /* copy the value of t and u into t0,u0 */ void copy_t_u(double t[3], double u[3][3], double t0[3], double u0[3][3]) { int i,j; for (i=0;i<3;i++) { t0[i]=t[i]; for (j=0;j<3;j++) u0[i][j]=u[i][j]; } } /* calculate approximate TM-score given rotation matrix */ double approx_TM(const int xlen, const int ylen, const int a_opt, double **xa, double **ya, double t[3], double u[3][3], const int invmap0[], const int mol_type) { double Lnorm_0=ylen; // normalized by the second protein if (a_opt==-2 && xlen>ylen) Lnorm_0=xlen; // longer else if (a_opt==-1 && xlen<ylen) Lnorm_0=xlen; // shorter else if (a_opt==1) Lnorm_0=(xlen+ylen)/2.; // average double D0_MIN; double Lnorm; double d0; double d0_search; parameter_set4final(Lnorm_0, D0_MIN, Lnorm, d0, d0_search, mol_type); double TMtmp=0; double d; double xtmp[3]={0,0,0}; for(int i=0,j=0; j<ylen; j++) { i=invmap0[j]; if(i>=0)//aligned { transform(t, u, &xa[i][0], &xtmp[0]); d=sqrt(dist(&xtmp[0], &ya[j][0])); TMtmp+=1/(1+(d/d0)*(d/d0)); //if (d <= score_d8) TMtmp+=1/(1+(d/d0)*(d/d0)); } } TMtmp/=Lnorm_0; return TMtmp; } void clean_up_after_approx_TM(int *invmap0, int *invmap, double **score, bool **path, double **val, double **xtm, double **ytm, double **xt, double **r1, double **r2, const int xlen, const int minlen) { delete [] invmap0; delete [] invmap; DeleteArray(&score, xlen+1); DeleteArray(&path, xlen+1); DeleteArray(&val, xlen+1); DeleteArray(&xtm, minlen); DeleteArray(&ytm, minlen); DeleteArray(&xt, xlen); DeleteArray(&r1, minlen); DeleteArray(&r2, minlen); return; } /* Entry function for TM-align. Return TM-score calculation status: * 0 - full TM-score calculation * 1 - terminated due to exception * 2-7 - pre-terminated due to low TM-score */ int TMalign_main(double **xa, double **ya, const char *seqx, const char *seqy, const char *secx, const char *secy, double t0[3], double u0[3][3], double &TM1, double &TM2, double &TM3, double &TM4, double &TM5, double &d0_0, double &TM_0, double &d0A, double &d0B, double &d0u, double &d0a, double &d0_out, string &seqM, string &seqxA, string &seqyA, double &rmsd0, int &L_ali, double &Liden, double &TM_ali, double &rmsd_ali, int &n_ali, int &n_ali8, const int xlen, const int ylen, const vector<string> sequence, const double Lnorm_ass, const double d0_scale, const int i_opt, const int a_opt, const bool u_opt, const bool d_opt, const bool fast_opt, const int mol_type, const double TMcut=-1) { double D0_MIN; //for d0 double Lnorm; //normalization length double score_d8,d0,d0_search,dcu0;//for TMscore search double t[3], u[3][3]; //Kabsch translation vector and rotation matrix double **score; // Input score table for dynamic programming bool **path; // for dynamic programming double **val; // for dynamic programming double **xtm, **ytm; // for TMscore search engine double **xt; //for saving the superposed version of r_1 or xtm double **r1, **r2; // for Kabsch rotation /***********************/ /* allocate memory */ /***********************/ int minlen = min(xlen, ylen); NewArray(&score, xlen+1, ylen+1); NewArray(&path, xlen+1, ylen+1); NewArray(&val, xlen+1, ylen+1); NewArray(&xtm, minlen, 3); NewArray(&ytm, minlen, 3); NewArray(&xt, xlen, 3); NewArray(&r1, minlen, 3); NewArray(&r2, minlen, 3); /***********************/ /* parameter set */ /***********************/ parameter_set4search(xlen, ylen, D0_MIN, Lnorm, score_d8, d0, d0_search, dcu0); int simplify_step = 40; //for similified search engine int score_sum_method = 8; //for scoring method, whether only sum over pairs with dis<score_d8 int i; int *invmap0 = new int[ylen+1]; int *invmap = new int[ylen+1]; double TM, TMmax=-1; for(i=0; i<ylen; i++) invmap0[i]=-1; double ddcc=0.4; if (Lnorm <= 40) ddcc=0.1; //Lnorm was setted in parameter_set4search double local_d0_search = d0_search; //************************************************// // get initial alignment from user's input: // // Stick to the initial alignment // //************************************************// bool bAlignStick = false; if (i_opt==3)// if input has set parameter for "-I" { // In the original code, this loop starts from 1, which is // incorrect. Fortran starts from 1 but C++ should starts from 0. for (int j = 0; j < ylen; j++)// Set aligned position to be "-1" invmap[j] = -1; int i1 = -1;// in C version, index starts from zero, not from one int i2 = -1; int L1 = sequence[0].size(); int L2 = sequence[1].size(); int L = min(L1, L2);// Get positions for aligned residues for (int kk1 = 0; kk1 < L; kk1++) { if (sequence[0][kk1] != '-') i1++; if (sequence[1][kk1] != '-') { i2++; if (i2 >= ylen || i1 >= xlen) kk1 = L; else if (sequence[0][kk1] != '-') invmap[i2] = i1; } } //--------------- 2. Align proteins from original alignment double prevD0_MIN = D0_MIN;// stored for later use int prevLnorm = Lnorm; double prevd0 = d0; TM_ali = standard_TMscore(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap, L_ali, rmsd_ali, D0_MIN, Lnorm, d0, d0_search, score_d8, t, u, mol_type); D0_MIN = prevD0_MIN; Lnorm = prevLnorm; d0 = prevd0; TM = detailed_search_standard(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap, t, u, 40, 8, local_d0_search, true, Lnorm, score_d8, d0); if (TM > TMmax) { TMmax = TM; for (i = 0; i<ylen; i++) invmap0[i] = invmap[i]; } bAlignStick = true; } /******************************************************/ /* get initial alignment with gapless threading */ /******************************************************/ if (!bAlignStick) { get_initial(r1, r2, xtm, ytm, xa, ya, xlen, ylen, invmap0, d0, d0_search, fast_opt, t, u); TM = detailed_search(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap0, t, u, simplify_step, score_sum_method, local_d0_search, Lnorm, score_d8, d0); if (TM>TMmax) TMmax = TM; if (TMcut>0) copy_t_u(t, u, t0, u0); //run dynamic programing iteratively to find the best alignment TM = DP_iter(r1, r2, xtm, ytm, xt, path, val, xa, ya, xlen, ylen, t, u, invmap, 0, 2, (fast_opt)?2:30, local_d0_search, D0_MIN, Lnorm, d0, score_d8); if (TM>TMmax) { TMmax = TM; for (int i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } if (TMcut>0) // pre-terminate if TM-score is too low { double TMtmp=approx_TM(xlen, ylen, a_opt, xa, ya, t0, u0, invmap0, mol_type); if (TMtmp<0.5*TMcut) { TM1=TM2=TM3=TM4=TM5=TMtmp; clean_up_after_approx_TM(invmap0, invmap, score, path, val, xtm, ytm, xt, r1, r2, xlen, minlen); return 2; } } /************************************************************/ /* get initial alignment based on secondary structure */ /************************************************************/ get_initial_ss(path, val, secx, secy, xlen, ylen, invmap); TM = detailed_search(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap, t, u, simplify_step, score_sum_method, local_d0_search, Lnorm, score_d8, d0); if (TM>TMmax) { TMmax = TM; for (int i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } if (TM > TMmax*0.2) { TM = DP_iter(r1, r2, xtm, ytm, xt, path, val, xa, ya, xlen, ylen, t, u, invmap, 0, 2, (fast_opt)?2:30, local_d0_search, D0_MIN, Lnorm, d0, score_d8); if (TM>TMmax) { TMmax = TM; for (int i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } } if (TMcut>0) // pre-terminate if TM-score is too low { double TMtmp=approx_TM(xlen, ylen, a_opt, xa, ya, t0, u0, invmap0, mol_type); if (TMtmp<0.52*TMcut) { TM1=TM2=TM3=TM4=TM5=TMtmp; clean_up_after_approx_TM(invmap0, invmap, score, path, val, xtm, ytm, xt, r1, r2, xlen, minlen); return 3; } } /************************************************************/ /* get initial alignment based on local superposition */ /************************************************************/ //=initial5 in original TM-align if (get_initial5( r1, r2, xtm, ytm, path, val, xa, ya, xlen, ylen, invmap, d0, d0_search, fast_opt, D0_MIN)) { TM = detailed_search(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap, t, u, simplify_step, score_sum_method, local_d0_search, Lnorm, score_d8, d0); if (TM>TMmax) { TMmax = TM; for (int i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } if (TM > TMmax*ddcc) { TM = DP_iter(r1, r2, xtm, ytm, xt, path, val, xa, ya, xlen, ylen, t, u, invmap, 0, 2, 2, local_d0_search, D0_MIN, Lnorm, d0, score_d8); if (TM>TMmax) { TMmax = TM; for (int i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } } } else cerr << "\n\nWarning: initial alignment from local superposition fail!\n\n" << endl; if (TMcut>0) // pre-terminate if TM-score is too low { double TMtmp=approx_TM(xlen, ylen, a_opt, xa, ya, t0, u0, invmap0, mol_type); if (TMtmp<0.54*TMcut) { TM1=TM2=TM3=TM4=TM5=TMtmp; clean_up_after_approx_TM(invmap0, invmap, score, path, val, xtm, ytm, xt, r1, r2, xlen, minlen); return 4; } } /********************************************************************/ /* get initial alignment by local superposition+secondary structure */ /********************************************************************/ //=initial3 in original TM-align get_initial_ssplus(r1, r2, score, path, val, secx, secy, xa, ya, xlen, ylen, invmap0, invmap, D0_MIN, d0); TM = detailed_search(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap, t, u, simplify_step, score_sum_method, local_d0_search, Lnorm, score_d8, d0); if (TM>TMmax) { TMmax = TM; for (i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } if (TM > TMmax*ddcc) { TM = DP_iter(r1, r2, xtm, ytm, xt, path, val, xa, ya, xlen, ylen, t, u, invmap, 0, 2, (fast_opt)?2:30, local_d0_search, D0_MIN, Lnorm, d0, score_d8); if (TM>TMmax) { TMmax = TM; for (i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } } if (TMcut>0) // pre-terminate if TM-score is too low { double TMtmp=approx_TM(xlen, ylen, a_opt, xa, ya, t0, u0, invmap0, mol_type); if (TMtmp<0.56*TMcut) { TM1=TM2=TM3=TM4=TM5=TMtmp; clean_up_after_approx_TM(invmap0, invmap, score, path, val, xtm, ytm, xt, r1, r2, xlen, minlen); return 5; } } /*******************************************************************/ /* get initial alignment based on fragment gapless threading */ /*******************************************************************/ //=initial4 in original TM-align get_initial_fgt(r1, r2, xtm, ytm, xa, ya, xlen, ylen, invmap, d0, d0_search, dcu0, fast_opt, t, u); TM = detailed_search(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap, t, u, simplify_step, score_sum_method, local_d0_search, Lnorm, score_d8, d0); if (TM>TMmax) { TMmax = TM; for (i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } if (TM > TMmax*ddcc) { TM = DP_iter(r1, r2, xtm, ytm, xt, path, val, xa, ya, xlen, ylen, t, u, invmap, 1, 2, 2, local_d0_search, D0_MIN, Lnorm, d0, score_d8); if (TM>TMmax) { TMmax = TM; for (i = 0; i<ylen; i++) invmap0[i] = invmap[i]; if (TMcut>0) copy_t_u(t, u, t0, u0); } } if (TMcut>0) // pre-terminate if TM-score is too low { double TMtmp=approx_TM(xlen, ylen, a_opt, xa, ya, t0, u0, invmap0, mol_type); if (TMtmp<0.58*TMcut) { TM1=TM2=TM3=TM4=TM5=TMtmp; clean_up_after_approx_TM(invmap0, invmap, score, path, val, xtm, ytm, xt, r1, r2, xlen, minlen); return 6; } } //************************************************// // get initial alignment from user's input: // //************************************************// if (i_opt==1)// if input has set parameter for "-i" { for (int j = 0; j < ylen; j++)// Set aligned position to be "-1" invmap[j] = -1; int i1 = -1;// in C version, index starts from zero, not from one int i2 = -1; int L1 = sequence[0].size(); int L2 = sequence[1].size(); int L = min(L1, L2);// Get positions for aligned residues for (int kk1 = 0; kk1 < L; kk1++) { if (sequence[0][kk1] != '-') i1++; if (sequence[1][kk1] != '-') { i2++; if (i2 >= ylen || i1 >= xlen) kk1 = L; else if (sequence[0][kk1] != '-') invmap[i2] = i1; } } //--------------- 2. Align proteins from original alignment double prevD0_MIN = D0_MIN;// stored for later use int prevLnorm = Lnorm; double prevd0 = d0; TM_ali = standard_TMscore(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap, L_ali, rmsd_ali, D0_MIN, Lnorm, d0, d0_search, score_d8, t, u, mol_type); D0_MIN = prevD0_MIN; Lnorm = prevLnorm; d0 = prevd0; TM = detailed_search_standard(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap, t, u, 40, 8, local_d0_search, true, Lnorm, score_d8, d0); if (TM > TMmax) { TMmax = TM; for (i = 0; i<ylen; i++) invmap0[i] = invmap[i]; } // Different from get_initial, get_initial_ss and get_initial_ssplus TM = DP_iter(r1, r2, xtm, ytm, xt, path, val, xa, ya, xlen, ylen, t, u, invmap, 0, 2, (fast_opt)?2:30, local_d0_search, D0_MIN, Lnorm, d0, score_d8); if (TM>TMmax) { TMmax = TM; for (i = 0; i<ylen; i++) invmap0[i] = invmap[i]; } } } //*******************************************************************// // The alignment will not be changed any more in the following // //*******************************************************************// //check if the initial alignment is generated approriately bool flag=false; for(i=0; i<ylen; i++) { if(invmap0[i]>=0) { flag=true; break; } } if(!flag) { cout << "There is no alignment between the two proteins!" << endl; cout << "Program stop with no result!" << endl; return 1; } /* last TM-score pre-termination */ if (TMcut>0) { double TMtmp=approx_TM(xlen, ylen, a_opt, xa, ya, t0, u0, invmap0, mol_type); if (TMtmp<0.6*TMcut) { TM1=TM2=TM3=TM4=TM5=TMtmp; clean_up_after_approx_TM(invmap0, invmap, score, path, val, xtm, ytm, xt, r1, r2, xlen, minlen); return 7; } } //********************************************************************// // Detailed TMscore search engine --> prepare for final TMscore // //********************************************************************// //run detailed TMscore search engine for the best alignment, and //extract the best rotation matrix (t, u) for the best alginment simplify_step=1; if (fast_opt) simplify_step=40; score_sum_method=8; TM = detailed_search_standard(r1, r2, xtm, ytm, xt, xa, ya, xlen, ylen, invmap0, t, u, simplify_step, score_sum_method, local_d0_search, false, Lnorm, score_d8, d0); //select pairs with dis<d8 for final TMscore computation and output alignment int k=0; int *m1, *m2; double d; m1=new int[xlen]; //alignd index in x m2=new int[ylen]; //alignd index in y do_rotation(xa, xt, xlen, t, u); k=0; for(int j=0; j<ylen; j++) { i=invmap0[j]; if(i>=0)//aligned { n_ali++; d=sqrt(dist(&xt[i][0], &ya[j][0])); if (d <= score_d8 || (i_opt == 3)) { m1[k]=i; m2[k]=j; xtm[k][0]=xa[i][0]; xtm[k][1]=xa[i][1]; xtm[k][2]=xa[i][2]; ytm[k][0]=ya[j][0]; ytm[k][1]=ya[j][1]; ytm[k][2]=ya[j][2]; r1[k][0] = xt[i][0]; r1[k][1] = xt[i][1]; r1[k][2] = xt[i][2]; r2[k][0] = ya[j][0]; r2[k][1] = ya[j][1]; r2[k][2] = ya[j][2]; k++; } } } n_ali8=k; Kabsch(r1, r2, n_ali8, 0, &rmsd0, t, u);// rmsd0 is used for final output, only recalculate rmsd0, not t & u rmsd0 = sqrt(rmsd0 / n_ali8); //****************************************// // Final TMscore // // Please set parameters for output // //****************************************// double rmsd; simplify_step=1; score_sum_method=0; double Lnorm_0=ylen; //normalized by length of structure A parameter_set4final(Lnorm_0, D0_MIN, Lnorm, d0, d0_search, mol_type); d0A=d0; d0_0=d0A; local_d0_search = d0_search; TM1 = TMscore8_search(r1, r2, xtm, ytm, xt, n_ali8, t0, u0, simplify_step, score_sum_method, &rmsd, local_d0_search, Lnorm, score_d8, d0); TM_0 = TM1; //normalized by length of structure B parameter_set4final(xlen+0.0, D0_MIN, Lnorm, d0, d0_search, mol_type); d0B=d0; local_d0_search = d0_search; TM2 = TMscore8_search(r1, r2, xtm, ytm, xt, n_ali8, t, u, simplify_step, score_sum_method, &rmsd, local_d0_search, Lnorm, score_d8, d0); double Lnorm_d0; if (a_opt>0) { //normalized by average length of structures A, B Lnorm_0=(xlen+ylen)*0.5; parameter_set4final(Lnorm_0, D0_MIN, Lnorm, d0, d0_search, mol_type); d0a=d0; d0_0=d0a; local_d0_search = d0_search; TM3 = TMscore8_search(r1, r2, xtm, ytm, xt, n_ali8, t0, u0, simplify_step, score_sum_method, &rmsd, local_d0_search, Lnorm, score_d8, d0); TM_0=TM3; } if (u_opt) { //normalized by user assigned length parameter_set4final(Lnorm_ass, D0_MIN, Lnorm, d0, d0_search, mol_type); d0u=d0; d0_0=d0u; Lnorm_0=Lnorm_ass; local_d0_search = d0_search; TM4 = TMscore8_search(r1, r2, xtm, ytm, xt, n_ali8, t0, u0, simplify_step, score_sum_method, &rmsd, local_d0_search, Lnorm, score_d8, d0); TM_0=TM4; } if (d_opt) { //scaled by user assigned d0 parameter_set4scale(ylen, d0_scale, Lnorm, d0, d0_search); d0_out=d0_scale; d0_0=d0_scale; //Lnorm_0=ylen; Lnorm_d0=Lnorm_0; local_d0_search = d0_search; TM5 = TMscore8_search(r1, r2, xtm, ytm, xt, n_ali8, t0, u0, simplify_step, score_sum_method, &rmsd, local_d0_search, Lnorm, score_d8, d0); TM_0=TM5; } /* derive alignment from superposition */ int ali_len=xlen+ylen; //maximum length of alignment seqxA.assign(ali_len,'-'); seqM.assign( ali_len,' '); seqyA.assign(ali_len,'-'); //do_rotation(xa, xt, xlen, t, u); do_rotation(xa, xt, xlen, t0, u0); int kk=0, i_old=0, j_old=0; d=0; for(int k=0; k<n_ali8; k++) { for(int i=i_old; i<m1[k]; i++) { //align x to gap seqxA[kk]=seqx[i]; seqyA[kk]='-'; seqM[kk]=' '; kk++; } for(int j=j_old; j<m2[k]; j++) { //align y to gap seqxA[kk]='-'; seqyA[kk]=seqy[j]; seqM[kk]=' '; kk++; } seqxA[kk]=seqx[m1[k]]; seqyA[kk]=seqy[m2[k]]; Liden+=(seqxA[kk]==seqyA[kk]); d=sqrt(dist(&xt[m1[k]][0], &ya[m2[k]][0])); if(d<d0_out) seqM[kk]=':'; else seqM[kk]='.'; kk++; i_old=m1[k]+1; j_old=m2[k]+1; } //tail for(int i=i_old; i<xlen; i++) { //align x to gap seqxA[kk]=seqx[i]; seqyA[kk]='-'; seqM[kk]=' '; kk++; } for(int j=j_old; j<ylen; j++) { //align y to gap seqxA[kk]='-'; seqyA[kk]=seqy[j]; seqM[kk]=' '; kk++; } seqxA=seqxA.substr(0,kk); seqyA=seqyA.substr(0,kk); seqM =seqM.substr(0,kk); /* free memory */ clean_up_after_approx_TM(invmap0, invmap, score, path, val, xtm, ytm, xt, r1, r2, xlen, minlen); delete [] m1; delete [] m2; return 0; // zero for no exception } /* entry function for TM-align with circular permutation * i_opt, a_opt, u_opt, d_opt, TMcut are not implemented yet */ int CPalign_main(double **xa, double **ya, const char *seqx, const char *seqy, const char *secx, const char *secy, double t0[3], double u0[3][3], double &TM1, double &TM2, double &TM3, double &TM4, double &TM5, double &d0_0, double &TM_0, double &d0A, double &d0B, double &d0u, double &d0a, double &d0_out, string &seqM, string &seqxA, string &seqyA, double &rmsd0, int &L_ali, double &Liden, double &TM_ali, double &rmsd_ali, int &n_ali, int &n_ali8, const int xlen, const int ylen, const vector<string> sequence, const double Lnorm_ass, const double d0_scale, const int i_opt, const int a_opt, const bool u_opt, const bool d_opt, const bool fast_opt, const int mol_type, const double TMcut=-1) { char *seqx_cp, *seqy_cp; // for the protein sequence char *secx_cp, *secy_cp; // for the secondary structure double **xa_cp, **ya_cp; // coordinates string seqxA_cp,seqyA_cp; // alignment int i,r; int cp_point=0; // position of circular permutation int cp_aln_best=0; // amount of aligned residue in sliding window int cp_aln_current;// amount of aligned residue in sliding window /* duplicate structure */ NewArray(&xa_cp, xlen*2, 3); seqx_cp = new char[xlen*2 + 1]; secx_cp = new char[xlen*2 + 1]; for (r=0;r<xlen;r++) { xa_cp[r+xlen][0]=xa_cp[r][0]=xa[r][0]; xa_cp[r+xlen][1]=xa_cp[r][1]=xa[r][1]; xa_cp[r+xlen][2]=xa_cp[r][2]=xa[r][2]; seqx_cp[r+xlen]=seqx_cp[r]=seqx[r]; secx_cp[r+xlen]=secx_cp[r]=secx[r]; } seqx_cp[2*xlen]=0; secx_cp[2*xlen]=0; /* fTM-align alignment */ double TM1_cp,TM2_cp; TMalign_main(xa_cp, ya, seqx_cp, seqy, secx_cp, secy, t0, u0, TM1_cp, TM2_cp, TM3, TM4, TM5, d0_0, TM_0, d0A, d0B, d0u, d0a, d0_out, seqM, seqxA_cp, seqyA_cp, rmsd0, L_ali, Liden, TM_ali, rmsd_ali, n_ali, n_ali8, xlen*2, ylen, sequence, Lnorm_ass, d0_scale, 0, false, false, false, true, mol_type, -1); /* delete gap in seqxA_cp */ r=0; seqxA=seqxA_cp; seqyA=seqyA_cp; for (i=0;i<seqxA_cp.size();i++) { if (seqxA_cp[i]!='-') { seqxA[r]=seqxA_cp[i]; seqyA[r]=seqyA_cp[i]; r++; } } seqxA=seqxA.substr(0,r); seqyA=seqyA.substr(0,r); /* count the number of aligned residues in each window * r - residue index in the original unaligned sequence * i - position in the alignment */ for (r=0;r<xlen-1;r++) { cp_aln_current=0; for (i=r;i<r+xlen;i++) cp_aln_current+=(seqyA[i]!='-'); if (cp_aln_current>cp_aln_best) { cp_aln_best=cp_aln_current; cp_point=r; } } seqM.clear(); seqxA.clear(); seqyA.clear(); seqxA_cp.clear(); seqyA_cp.clear(); rmsd0=Liden=n_ali=n_ali8=0; /* fTM-align alignment */ TMalign_main(xa, ya, seqx, seqy, secx, secy, t0, u0, TM1, TM2, TM3, TM4, TM5, d0_0, TM_0, d0A, d0B, d0u, d0a, d0_out, seqM, seqxA, seqyA, rmsd0, L_ali, Liden, TM_ali, rmsd_ali, n_ali, n_ali8, xlen, ylen, sequence, Lnorm_ass, d0_scale, 0, false, false, false, true, mol_type, -1); /* do not use cricular permutation of number of aligned residues is not * larger than sequence-order dependent alignment */ if (n_ali8>cp_aln_best) cp_point=0; /* prepare structure for final alignment */ seqM.clear(); seqxA.clear(); seqyA.clear(); rmsd0=Liden=n_ali=n_ali8=0; if (cp_point!=0) { for (r=0;r<xlen;r++) { xa_cp[r][0]=xa_cp[r+cp_point][0]; xa_cp[r][1]=xa_cp[r+cp_point][1]; xa_cp[r][2]=xa_cp[r+cp_point][2]; seqx_cp[r]=seqx_cp[r+cp_point]; secx_cp[r]=secx_cp[r+cp_point]; } } seqx_cp[xlen]=0; secx_cp[xlen]=0; /* full TM-align */ TMalign_main(xa_cp, ya, seqx_cp, seqy, secx_cp, secy, t0, u0, TM1, TM2, TM3, TM4, TM5, d0_0, TM_0, d0A, d0B, d0u, d0a, d0_out, seqM, seqxA_cp, seqyA_cp, rmsd0, L_ali, Liden, TM_ali, rmsd_ali, n_ali, n_ali8, xlen, ylen, sequence, Lnorm_ass, d0_scale, i_opt, a_opt, u_opt, d_opt, fast_opt, mol_type, TMcut); /* correct alignment * r - residue index in the original unaligned sequence * i - position in the alignment */ if (cp_point>0) { r=0; for (i=0;i<seqxA_cp.size();i++) { r+=(seqxA_cp[i]!='-'); if (r>=(xlen-cp_point)) { i++; break; } } seqxA=seqxA_cp.substr(0,i)+'*'+seqxA_cp.substr(i); seqM =seqM.substr(0,i) +' '+seqM.substr(i); seqyA=seqyA_cp.substr(0,i)+'-'+seqyA_cp.substr(i); } else { seqxA=seqxA_cp; seqyA=seqyA_cp; } /* clean up */ delete[]seqx_cp; delete[]secx_cp; DeleteArray(&xa_cp,xlen*2); seqxA_cp.clear(); seqyA_cp.clear(); return cp_point; } int main(int argc, char *argv[]) { if (argc < 2) print_help(); clock_t t1, t2; t1 = clock(); /**********************/ /* get argument */ /**********************/ string xname = ""; string yname = ""; string fname_super = ""; // file name for superposed structure string fname_lign = ""; // file name for user alignment string fname_matrix= ""; // file name for output matrix vector<string> sequence; // get value from alignment file double Lnorm_ass, d0_scale; bool h_opt = false; // print full help message bool v_opt = false; // print version bool m_opt = false; // flag for -m, output rotation matrix int i_opt = 0; // 1 for -i, 3 for -I bool o_opt = false; // flag for -o, output superposed structure int a_opt = 0; // flag for -a, do not normalized by average length bool u_opt = false; // flag for -u, normalized by user specified length bool d_opt = false; // flag for -d, user specified d0 double TMcut =-1; int infmt1_opt=-1; // PDB or PDBx/mmCIF format for chain_1 int infmt2_opt=-1; // PDB or PDBx/mmCIF format for chain_2 int ter_opt =3; // TER, END, or different chainID int split_opt =0; // do not split chain int outfmt_opt=0; // set -outfmt to full output bool fast_opt =false; // flags for -fast, fTM-align algorithm int cp_opt =0; // do not check circular permutation int mirror_opt=0; // do not align mirror int het_opt=0; // do not read HETATM residues string atom_opt ="auto";// use C alpha atom for protein and C3' for RNA string mol_opt ="auto";// auto-detect the molecule type as protein/RNA string suffix_opt=""; // set -suffix to empty string dir_opt =""; // set -dir to empty string dir1_opt =""; // set -dir1 to empty string dir2_opt =""; // set -dir2 to empty int byresi_opt=0; // set -byresi to 0 vector<string> chain1_list; // only when -dir1 is set vector<string> chain2_list; // only when -dir2 is set for(int i = 1; i < argc; i++) { if ( !strcmp(argv[i],"-o") && i < (argc-1) ) { fname_super = argv[i + 1]; o_opt = true; i++; } else if ( (!strcmp(argv[i],"-u") || !strcmp(argv[i],"-L")) && i < (argc-1) ) { Lnorm_ass = atof(argv[i + 1]); u_opt = true; i++; } else if ( !strcmp(argv[i],"-a") && i < (argc-1) ) { if (!strcmp(argv[i + 1], "T")) a_opt=true; else if (!strcmp(argv[i + 1], "F")) a_opt=false; else { a_opt=atoi(argv[i + 1]); if (a_opt!=-2 && a_opt!=-1 && a_opt!=1) PrintErrorAndQuit("-a must be -2, -1, 1, T or F"); } i++; } else if ( !strcmp(argv[i],"-d") && i < (argc-1) ) { d0_scale = atof(argv[i + 1]); d_opt = true; i++; } else if ( !strcmp(argv[i],"-v") ) { v_opt = true; } else if ( !strcmp(argv[i],"-h") ) { h_opt = true; } else if ( !strcmp(argv[i],"-i") && i < (argc-1) ) { if (i_opt==3) PrintErrorAndQuit("ERROR! -i and -I cannot be used together"); fname_lign = argv[i + 1]; i_opt = 1; i++; } else if (!strcmp(argv[i], "-I") && i < (argc-1) ) { if (i_opt==1) PrintErrorAndQuit("ERROR! -I and -i cannot be used together"); fname_lign = argv[i + 1]; i_opt = 3; i++; } else if (!strcmp(argv[i], "-m") && i < (argc-1) ) { fname_matrix = argv[i + 1]; m_opt = true; i++; }// get filename for rotation matrix else if (!strcmp(argv[i], "-fast")) { fast_opt = true; } else if ( !strcmp(argv[i],"-infmt1") && i < (argc-1) ) { infmt1_opt=atoi(argv[i + 1]); i++; } else if ( !strcmp(argv[i],"-infmt2") && i < (argc-1) ) { infmt2_opt=atoi(argv[i + 1]); i++; } else if ( !strcmp(argv[i],"-ter") && i < (argc-1) ) { ter_opt=atoi(argv[i + 1]); i++; } else if ( !strcmp(argv[i],"-split") && i < (argc-1) ) { split_opt=atoi(argv[i + 1]); i++; } else if ( !strcmp(argv[i],"-atom") && i < (argc-1) ) { atom_opt=argv[i + 1]; i++; } else if ( !strcmp(argv[i],"-mol") && i < (argc-1) ) { mol_opt=argv[i + 1]; i++; } else if ( !strcmp(argv[i],"-dir") && i < (argc-1) ) { dir_opt=argv[i + 1]; i++; } else if ( !strcmp(argv[i],"-dir1") && i < (argc-1) ) { dir1_opt=argv[i + 1]; i++; } else if ( !strcmp(argv[i],"-dir2") && i < (argc-1) ) { dir2_opt=argv[i + 1]; i++; } else if ( !strcmp(argv[i],"-suffix") && i < (argc-1) ) { suffix_opt=argv[i + 1]; i++; } else if ( !strcmp(argv[i],"-outfmt") && i < (argc-1) ) { outfmt_opt=atoi(argv[i + 1]); i++; } else if ( !strcmp(argv[i],"-TMcut") && i < (argc-1) ) { TMcut=atof(argv[i + 1]); i++; } else if ( !strcmp(argv[i],"-byresi") && i < (argc-1) ) { byresi_opt=atoi(argv[i + 1]); i++; } else if ( !strcmp(argv[i],"-cp") ) { cp_opt=1; } else if ( !strcmp(argv[i],"-mirror") && i < (argc-1) ) { mirror_opt=atoi(argv[i + 1]); i++; } else if ( !strcmp(argv[i],"-het") && i < (argc-1) ) { het_opt=atoi(argv[i + 1]); i++; } else if (xname.size() == 0) xname=argv[i]; else if (yname.size() == 0) yname=argv[i]; else PrintErrorAndQuit(string("ERROR! Undefined option ")+argv[i]); } if(xname.size()==0 || (yname.size()==0 && dir_opt.size()==0) || (yname.size() && dir_opt.size())) { if (h_opt) print_help(h_opt); if (v_opt) { print_version(); exit(EXIT_FAILURE); } if (xname.size()==0) PrintErrorAndQuit("Please provide input structures"); else if (yname.size()==0 && dir_opt.size()==0) PrintErrorAndQuit("Please provide structure B"); else if (yname.size() && dir_opt.size()) PrintErrorAndQuit("Please provide only one file name if -dir is set"); } if (suffix_opt.size() && dir_opt.size()+dir1_opt.size()+dir2_opt.size()==0) PrintErrorAndQuit("-suffix is only valid if -dir, -dir1 or -dir2 is set"); if ((dir_opt.size() || dir1_opt.size() || dir2_opt.size())) { if (m_opt || o_opt) PrintErrorAndQuit("-m or -o cannot be set with -dir, -dir1 or -dir2"); else if (dir_opt.size() && (dir1_opt.size() || dir2_opt.size())) PrintErrorAndQuit("-dir cannot be set with -dir1 or -dir2"); } if (atom_opt.size()!=4) PrintErrorAndQuit("ERROR! atom name must have 4 characters, including space."); if (mol_opt!="auto" && mol_opt!="protein" && mol_opt!="RNA") PrintErrorAndQuit("ERROR! molecule type must be either RNA or protein."); else if (mol_opt=="protein" && atom_opt=="auto") atom_opt=" CA "; else if (mol_opt=="RNA" && atom_opt=="auto") atom_opt=" C3'"; if (u_opt && Lnorm_ass<=0) PrintErrorAndQuit("Wrong value for option -u! It should be >0"); if (d_opt && d0_scale<=0) PrintErrorAndQuit("Wrong value for option -d! It should be >0"); if (outfmt_opt>=2 && (a_opt || u_opt || d_opt)) PrintErrorAndQuit("-outfmt 2 cannot be used with -a, -u, -L, -d"); if (byresi_opt!=0) { if (i_opt) PrintErrorAndQuit("-byresi >=1 cannot be used with -i or -I"); if (byresi_opt<0 || byresi_opt>3) PrintErrorAndQuit("-byresi can only be 0, 1, 2 or 3"); if (byresi_opt>=2 && ter_opt>=2) PrintErrorAndQuit("-byresi >=2 should be used with -ter <=1"); } if (split_opt==1 && ter_opt!=0) PrintErrorAndQuit("-split 1 should be used with -ter 0"); else if (split_opt==2 && ter_opt!=0 && ter_opt!=1) PrintErrorAndQuit("-split 2 should be used with -ter 0 or 1"); if (split_opt<0 || split_opt>2) PrintErrorAndQuit("-split can only be 0, 1 or 2"); if (cp_opt!=0 && cp_opt!=1) PrintErrorAndQuit("-cp can only be 0 or 1"); if (cp_opt && i_opt) PrintErrorAndQuit("-cp cannot be used with -i or -I"); /* read initial alignment file from 'align.txt' */ if (i_opt) read_user_alignment(sequence, fname_lign, i_opt); if (byresi_opt) i_opt=3; if (m_opt && fname_matrix == "") // Output rotation matrix: matrix.txt PrintErrorAndQuit("ERROR! Please provide a file name for option -m!"); /* parse file list */ if (dir1_opt.size()+dir_opt.size()==0) chain1_list.push_back(xname); else file2chainlist(chain1_list, xname, dir_opt+dir1_opt, suffix_opt); if (dir_opt.size()) for (int i=0;i<chain1_list.size();i++) chain2_list.push_back(chain1_list[i]); else if (dir2_opt.size()==0) chain2_list.push_back(yname); else file2chainlist(chain2_list, yname, dir2_opt, suffix_opt); if (outfmt_opt==2) cout<<"#PDBchain1\tPDBchain2\tTM1\tTM2\t" <<"RMSD\tID1\tID2\tIDali\tL1\tL2\tLali"<<endl; /* declare previously global variables */ vector<vector<string> >PDB_lines1; // text of chain1 vector<vector<string> >PDB_lines2; // text of chain2 vector<int> mol_vec1; // molecule type of chain1, RNA if >0 vector<int> mol_vec2; // molecule type of chain2, RNA if >0 vector<string> chainID_list1; // list of chainID1 vector<string> chainID_list2; // list of chainID2 int i,j; // file index int chain_i,chain_j; // chain index int r; // residue index int xlen, ylen; // chain length int xchainnum,ychainnum;// number of chains in a PDB file char *seqx, *seqy; // for the protein sequence char *secx, *secy; // for the secondary structure double **xa, **ya; // for input vectors xa[0...xlen-1][0..2] and // ya[0...ylen-1][0..2], in general, // ya is regarded as native structure // --> superpose xa onto ya vector<string> resi_vec1; // residue index for chain1 vector<string> resi_vec2; // residue index for chain2 /* loop over file names */ for (i=0;i<chain1_list.size();i++) { /* parse chain 1 */ xname=chain1_list[i]; xchainnum=get_PDB_lines(xname, PDB_lines1, chainID_list1, mol_vec1, ter_opt, infmt1_opt, atom_opt, split_opt, het_opt); if (!xchainnum) { cerr<<"Warning! Cannot parse file: "<<xname <<". Chain number 0."<<endl; continue; } for (chain_i=0;chain_i<xchainnum;chain_i++) { xlen=PDB_lines1[chain_i].size(); mol_vec1[chain_i]=-1; if (!xlen) { cerr<<"Warning! Cannot parse file: "<<xname <<". Chain length 0."<<endl; continue; } else if (xlen<3) { cerr<<"Sequence is too short <3!: "<<xname<<endl; continue; } NewArray(&xa, xlen, 3); seqx = new char[xlen + 1]; secx = new char[xlen + 1]; xlen = read_PDB(PDB_lines1[chain_i], xa, seqx, resi_vec1, byresi_opt?byresi_opt:o_opt); if (mirror_opt) for (r=0;r<xlen;r++) xa[r][2]=-xa[r][2]; make_sec(xa, xlen, secx); // secondary structure assignment for (j=(dir_opt.size()>0)*(i+1);j<chain2_list.size();j++) { /* parse chain 2 */ if (PDB_lines2.size()==0) { yname=chain2_list[j]; ychainnum=get_PDB_lines(yname, PDB_lines2, chainID_list2, mol_vec2, ter_opt, infmt2_opt, atom_opt, split_opt, het_opt); if (!ychainnum) { cerr<<"Warning! Cannot parse file: "<<yname <<". Chain number 0."<<endl; continue; } } for (chain_j=0;chain_j<ychainnum;chain_j++) { ylen=PDB_lines2[chain_j].size(); mol_vec2[chain_j]=-1; if (!ylen) { cerr<<"Warning! Cannot parse file: "<<yname <<". Chain length 0."<<endl; continue; } else if (ylen<3) { cerr<<"Sequence is too short <3!: "<<yname<<endl; continue; } NewArray(&ya, ylen, 3); seqy = new char[ylen + 1]; secy = new char[ylen + 1]; ylen = read_PDB(PDB_lines2[chain_j], ya, seqy, resi_vec2, byresi_opt?byresi_opt:o_opt); make_sec(ya, ylen, secy); if (byresi_opt) extract_aln_from_resi(sequence, seqx,seqy,resi_vec1,resi_vec2,byresi_opt); /* declare variable specific to this pair of TMalign */ double t0[3], u0[3][3]; double TM1, TM2; double TM3, TM4, TM5; // for a_opt, u_opt, d_opt double d0_0, TM_0; double d0A, d0B, d0u, d0a; double d0_out=5.0; string seqM, seqxA, seqyA;// for output alignment double rmsd0 = 0.0; int L_ali; // Aligned length in standard_TMscore double Liden=0; double TM_ali, rmsd_ali; // TMscore and rmsd in standard_TMscore int n_ali=0; int n_ali8=0; /* entry function for structure alignment */ if (cp_opt) CPalign_main( xa, ya, seqx, seqy, secx, secy, t0, u0, TM1, TM2, TM3, TM4, TM5, d0_0, TM_0, d0A, d0B, d0u, d0a, d0_out, seqM, seqxA, seqyA, rmsd0, L_ali, Liden, TM_ali, rmsd_ali, n_ali, n_ali8, xlen, ylen, sequence, Lnorm_ass, d0_scale, i_opt, a_opt, u_opt, d_opt, fast_opt, mol_vec1[chain_i]+mol_vec2[chain_j],TMcut); else TMalign_main( xa, ya, seqx, seqy, secx, secy, t0, u0, TM1, TM2, TM3, TM4, TM5, d0_0, TM_0, d0A, d0B, d0u, d0a, d0_out, seqM, seqxA, seqyA, rmsd0, L_ali, Liden, TM_ali, rmsd_ali, n_ali, n_ali8, xlen, ylen, sequence, Lnorm_ass, d0_scale, i_opt, a_opt, u_opt, d_opt, fast_opt, mol_vec1[chain_i]+mol_vec2[chain_j],TMcut); /* print result */ if (outfmt_opt==0) print_version(); output_results( xname.substr(dir1_opt.size()), yname.substr(dir2_opt.size()), chainID_list1[chain_i].c_str(), chainID_list2[chain_j].c_str(), xlen, ylen, t0, u0, TM1, TM2, TM3, TM4, TM5, rmsd0, d0_out, seqM.c_str(), seqxA.c_str(), seqyA.c_str(), Liden, n_ali8, L_ali, TM_ali, rmsd_ali, TM_0, d0_0, d0A, d0B, Lnorm_ass, d0_scale, d0a, d0u, (m_opt?fname_matrix+chainID_list1[chain_i]:"").c_str(), outfmt_opt, ter_opt, (o_opt?fname_super+chainID_list1[chain_i]:"").c_str(), i_opt, a_opt, u_opt, d_opt,mirror_opt, resi_vec1,resi_vec2); /* Done! Free memory */ seqM.clear(); seqxA.clear(); seqyA.clear(); DeleteArray(&ya, ylen); delete [] seqy; delete [] secy; resi_vec2.clear(); } // chain_j if (chain2_list.size()>1) { yname.clear(); for (chain_j=0;chain_j<ychainnum;chain_j++) PDB_lines2[chain_j].clear(); PDB_lines2.clear(); chainID_list2.clear(); mol_vec2.clear(); } } // j PDB_lines1[chain_i].clear(); DeleteArray(&xa, xlen); delete [] seqx; delete [] secx; resi_vec1.clear(); } // chain_i xname.clear(); PDB_lines1.clear(); chainID_list1.clear(); mol_vec1.clear(); } // i if (chain2_list.size()==1) { yname.clear(); for (chain_j=0;chain_j<ychainnum;chain_j++) PDB_lines2[chain_j].clear(); PDB_lines2.clear(); resi_vec2.clear(); chainID_list2.clear(); mol_vec2.clear(); } chain1_list.clear(); chain2_list.clear(); sequence.clear(); t2 = clock(); float diff = ((float)t2 - (float)t1)/CLOCKS_PER_SEC; printf("Total CPU time is %5.2f seconds\n", diff); return 0; }