Mercurial > repos > bgruening > enumerate_charges
changeset 5:67ee76f0e497 draft default tip
"planemo upload for repository https://github.com/bgruening/galaxytools/tree/master/chemicaltoolbox/rdkit commit c1d813d3f0fec60ea6efe8a11e59d98bfdc1636f"
| author | bgruening |
|---|---|
| date | Sat, 04 Dec 2021 16:40:23 +0000 |
| parents | bbbf5fb356dd |
| children | |
| files | dimorphite_dl.py rdconf.py rdkit_descriptors.py sdf_to_tab.py test-data/rdconf_output.sdf test-data/staurosporine.smi |
| diffstat | 6 files changed, 846 insertions(+), 177 deletions(-) [+] |
line wrap: on
line diff
--- a/dimorphite_dl.py Wed Feb 17 12:59:24 2021 +0000 +++ b/dimorphite_dl.py Sat Dec 04 16:40:23 2021 +0000 @@ -19,8 +19,9 @@ """ from __future__ import print_function + +import argparse import os -import argparse import sys try: @@ -43,11 +44,12 @@ import rdkit from rdkit import Chem from rdkit.Chem import AllChem -except: +except Exception: msg = "Dimorphite-DL requires RDKit. See https://www.rdkit.org/" print(msg) raise Exception(msg) + def main(params=None): """The main definition run when you call the script from the commandline. @@ -84,13 +86,14 @@ with open(args["output_file"], "w") as file: for protonated_smi in Protonate(args): file.write(protonated_smi + "\n") - elif "return_as_list" in args and args["return_as_list"] == True: + elif "return_as_list" in args and args["return_as_list"]: return list(Protonate(args)) else: # No output file specified. Just print it to the screen. for protonated_smi in Protonate(args): print(protonated_smi) + class MyParser(argparse.ArgumentParser): """Overwrite default parse so it displays help file on error. See https://stackoverflow.com/questions/4042452/display-help-message-with-python-argparse-when-script-is-called-without-any-argu""" @@ -117,15 +120,18 @@ if file is None: file = sys.stdout self._print_message(self.format_help(), file) - print(""" + print( + """ examples: python dimorphite_dl.py --smiles_file sample_molecules.smi python dimorphite_dl.py --smiles "CCC(=O)O" --min_ph -3.0 --max_ph -2.0 python dimorphite_dl.py --smiles "CCCN" --min_ph -3.0 --max_ph -2.0 --output_file output.smi python dimorphite_dl.py --smiles_file sample_molecules.smi --pka_precision 2.0 --label_states - python dimorphite_dl.py --test""") + python dimorphite_dl.py --test""" + ) print("") + class ArgParseFuncs: """A namespace for storing functions that are useful for processing command-line arguments. To keep things organized.""" @@ -137,27 +143,57 @@ :return: A parser object. """ - parser = MyParser(description="Dimorphite 1.2: Creates models of " + - "appropriately protonated small moleucles. " + - "Apache 2.0 License. Copyright 2018 Jacob D. " + - "Durrant.") - parser.add_argument('--min_ph', metavar='MIN', type=float, default=6.4, - help='minimum pH to consider (default: 6.4)') - parser.add_argument('--max_ph', metavar='MAX', type=float, default=8.4, - help='maximum pH to consider (default: 8.4)') - parser.add_argument('--pka_precision', metavar='PRE', type=float, default=1.0, - help='pKa precision factor (number of standard devations, default: 1.0)') - parser.add_argument('--smiles', metavar='SMI', type=str, - help='SMILES string to protonate') - parser.add_argument('--smiles_file', metavar="FILE", type=str, - help='file that contains SMILES strings to protonate') - parser.add_argument('--output_file', metavar="FILE", type=str, - help='output file to write protonated SMILES (optional)') - parser.add_argument('--label_states', action="store_true", - help='label protonated SMILES with target state ' + \ - '(i.e., "DEPROTONATED", "PROTONATED", or "BOTH").') - parser.add_argument('--test', action="store_true", - help='run unit tests (for debugging)') + parser = MyParser( + description="Dimorphite 1.2: Creates models of " + + "appropriately protonated small moleucles. " + + "Apache 2.0 License. Copyright 2018 Jacob D. " + + "Durrant." + ) + parser.add_argument( + "--min_ph", + metavar="MIN", + type=float, + default=6.4, + help="minimum pH to consider (default: 6.4)", + ) + parser.add_argument( + "--max_ph", + metavar="MAX", + type=float, + default=8.4, + help="maximum pH to consider (default: 8.4)", + ) + parser.add_argument( + "--pka_precision", + metavar="PRE", + type=float, + default=1.0, + help="pKa precision factor (number of standard devations, default: 1.0)", + ) + parser.add_argument( + "--smiles", metavar="SMI", type=str, help="SMILES string to protonate" + ) + parser.add_argument( + "--smiles_file", + metavar="FILE", + type=str, + help="file that contains SMILES strings to protonate", + ) + parser.add_argument( + "--output_file", + metavar="FILE", + type=str, + help="output file to write protonated SMILES (optional)", + ) + parser.add_argument( + "--label_states", + action="store_true", + help="label protonated SMILES with target state " + + '(i.e., "DEPROTONATED", "PROTONATED", or "BOTH").', + ) + parser.add_argument( + "--test", action="store_true", help="run unit tests (for debugging)" + ) return parser @@ -170,11 +206,13 @@ :raises Exception: No SMILES in params. """ - defaults = {'min_ph' : 6.4, - 'max_ph' : 8.4, - 'pka_precision' : 1.0, - 'label_states' : False, - 'test' : False} + defaults = { + "min_ph": 6.4, + "max_ph": 8.4, + "pka_precision": 1.0, + "label_states": False, + "test": False, + } for key in defaults: if key not in args: @@ -194,12 +232,13 @@ # object. if "smiles" in args: if isinstance(args["smiles"], str): - args["smiles_file"] = StringIO(args["smiles"]) + args["smiles_file"] = StringIO(args["smiles"]) args["smiles_and_data"] = LoadSMIFile(args["smiles_file"]) return args + class UtilFuncs: """A namespace to store functions for manipulating mol objects. To keep things organized.""" @@ -215,15 +254,33 @@ # Get the reaction data rxn_data = [ - ['[Ov1-1:1]', '[Ov2+0:1]-[H]'], # To handle O- bonded to only one atom (add hydrogen). - ['[#7v4+1:1]-[H]', '[#7v3+0:1]'], # To handle N+ bonded to a hydrogen (remove hydrogen). - ['[Ov2-:1]', '[Ov2+0:1]'], # To handle O- bonded to two atoms. Should not be Negative. - ['[#7v3+1:1]', '[#7v3+0:1]'], # To handle N+ bonded to three atoms. Should not be positive. - ['[#7v2-1:1]', '[#7+0:1]-[H]'], # To handle N- Bonded to two atoms. Add hydrogen. + [ + "[Ov1-1:1]", + "[Ov2+0:1]-[H]", + ], # To handle O- bonded to only one atom (add hydrogen). + [ + "[#7v4+1:1]-[H]", + "[#7v3+0:1]", + ], # To handle N+ bonded to a hydrogen (remove hydrogen). + [ + "[Ov2-:1]", + "[Ov2+0:1]", + ], # To handle O- bonded to two atoms. Should not be Negative. + [ + "[#7v3+1:1]", + "[#7v3+0:1]", + ], # To handle N+ bonded to three atoms. Should not be positive. + [ + "[#7v2-1:1]", + "[#7+0:1]-[H]", + ], # To handle N- Bonded to two atoms. Add hydrogen. # ['[N:1]=[N+0:2]=[N:3]-[H]', '[N:1]=[N+1:2]=[N+0:3]-[H]'], # To # handle bad azide. Must be protonated. (Now handled elsewhere, before # SMILES converted to Mol object.) - ['[H]-[N:1]-[N:2]#[N:3]', '[N:1]=[N+1:2]=[N:3]-[H]'] # To handle bad azide. R-N-N#N should be R-N=[N+]=N + [ + "[H]-[N:1]-[N:2]#[N:3]", + "[N:1]=[N+1:2]=[N:3]-[H]", + ], # To handle bad azide. R-N-N#N should be R-N=[N+]=N ] # Add substructures and reactions (initially none) @@ -241,10 +298,15 @@ current_rxn_str = None for i, rxn_datum in enumerate(rxn_data): - reactant_smarts, product_smarts, substruct_match_mol, rxn_placeholder = rxn_datum + ( + reactant_smarts, + product_smarts, + substruct_match_mol, + rxn_placeholder, + ) = rxn_datum if mol.HasSubstructMatch(substruct_match_mol): if rxn_placeholder is None: - current_rxn_str = reactant_smarts + '>>' + product_smarts + current_rxn_str = reactant_smarts + ">>" + product_smarts current_rxn = AllChem.ReactionFromSmarts(current_rxn_str) rxn_data[i][3] = current_rxn # Update the placeholder. else: @@ -262,10 +324,10 @@ # to resanitize them. Make sure aromatic rings are shown as such This # catches all RDKit Errors. without the catchError and sanitizeOps the # Chem.SanitizeMol can crash the program. - sanitize_string = Chem.SanitizeMol( + sanitize_string = Chem.SanitizeMol( mol, sanitizeOps=rdkit.Chem.rdmolops.SanitizeFlags.SANITIZE_ALL, - catchErrors = True + catchErrors=True, ) return mol if sanitize_string.name == "SANITIZE_NONE" else None @@ -321,6 +383,7 @@ print(*args, file=sys.stderr, **kwargs) + class LoadSMIFile(object): """A generator class for loading in the SMILES strings from a file, one at a time.""" @@ -388,37 +451,43 @@ # into a canonical form. Filter if failed. mol = UtilFuncs.convert_smiles_str_to_mol(smiles_str) if mol is None: - UtilFuncs.eprint("WARNING: Skipping poorly formed SMILES string: " + line) + UtilFuncs.eprint( + "WARNING: Skipping poorly formed SMILES string: " + line + ) return self.next() # Handle nuetralizing the molecules. Filter if failed. mol = UtilFuncs.neutralize_mol(mol) if mol is None: - UtilFuncs.eprint("WARNING: Skipping poorly formed SMILES string: " + line) + UtilFuncs.eprint( + "WARNING: Skipping poorly formed SMILES string: " + line + ) return self.next() # Remove the hydrogens. try: mol = Chem.RemoveHs(mol) - except: - UtilFuncs.eprint("WARNING: Skipping poorly formed SMILES string: " + line) + except Exception: + UtilFuncs.eprint( + "WARNING: Skipping poorly formed SMILES string: " + line + ) return self.next() if mol is None: - UtilFuncs.eprint("WARNING: Skipping poorly formed SMILES string: " + line) + UtilFuncs.eprint( + "WARNING: Skipping poorly formed SMILES string: " + line + ) return self.next() # Regenerate the smiles string (to standardize). new_mol_string = Chem.MolToSmiles(mol, isomericSmiles=True) - return { - "smiles": new_mol_string, - "data": splits[1:] - } + return {"smiles": new_mol_string, "data": splits[1:]} else: # Blank line? Go to next one. return self.next() + class Protonate(object): """A generator class for protonating SMILES strings, one at a time.""" @@ -491,8 +560,8 @@ smi = smile_and_datum["smiles"] data = smile_and_datum["data"] # Everything on SMILES line but the - # SMILES string itself (e.g., the - # molecule name). + # SMILES string itself (e.g., the + # molecule name). # Collect the data associated with this smiles (e.g., the molecule # name). @@ -516,8 +585,8 @@ # Only add new smiles if not already in the list. # for s in new_smis_to_perhaps_add: - # if not s in new_smis: - # new_smis.append(s) + # if not s in new_smis: + # new_smis.append(s) # In some cases, the script might generate redundant molecules. # Phosphonates, when the pH is between the two pKa values and the @@ -532,7 +601,9 @@ # Sometimes Dimorphite-DL generates molecules that aren't actually # possible. Simply convert these to mol objects to eliminate the bad # ones (that are None). - new_smis = [s for s in new_smis if UtilFuncs.convert_smiles_str_to_mol(s) is not None] + new_smis = [ + s for s in new_smis if UtilFuncs.convert_smiles_str_to_mol(s) is not None + ] # If there are no smi left, return the input one at the very least. # All generated forms have apparently been judged @@ -543,7 +614,7 @@ # If the user wants to see the target states, add those # to the ends of each line. if self.args["label_states"]: - states = '\t'.join([x[1] for x in sites]) + states = "\t".join([x[1] for x in sites]) new_lines = [x + "\t" + tag + "\t" + states for x in new_smis] else: new_lines = [x + "\t" + tag for x in new_smis] @@ -552,12 +623,15 @@ return self.next() + class ProtSubstructFuncs: """A namespace to store functions for loading the substructures that can be protonated. To keep things organized.""" @staticmethod - def load_protonation_substructs_calc_state_for_ph(min_ph=6.4, max_ph=8.4, pka_std_range=1): + def load_protonation_substructs_calc_state_for_ph( + min_ph=6.4, max_ph=8.4, pka_std_range=1 + ): """A pre-calculated list of R-groups with protonation sites, with their likely pKa bins. @@ -573,7 +647,7 @@ pwd = os.path.dirname(os.path.realpath(__file__)) site_structures_file = "{}/{}".format(pwd, "site_substructures.smarts") - with open(site_structures_file, 'r') as substruct: + with open(site_structures_file, "r") as substruct: for line in substruct: line = line.strip() sub = {} @@ -584,7 +658,9 @@ sub["mol"] = Chem.MolFromSmarts(sub["smart"]) # NEED TO DIVIDE THIS BY 3s - pka_ranges = [splits[i:i+3] for i in range(2, len(splits)-1, 3)] + pka_ranges = [ + splits[i : i + 3] for i in range(2, len(splits) - 1, 3) + ] prot = [] for pka_range in pka_ranges: @@ -620,11 +696,11 @@ # This needs to be reassigned, and 'ERROR' should never make it past the # next set of checks. if min_pka <= max_ph and min_ph <= max_pka: - protonation_state = 'BOTH' + protonation_state = "BOTH" elif mean > max_ph: - protonation_state = 'PROTONATED' + protonation_state = "PROTONATED" else: - protonation_state = 'DEPROTONATED' + protonation_state = "DEPROTONATED" return protonation_state @@ -650,8 +726,8 @@ # Try to Add hydrogens. if failed return [] try: - mol = Chem.AddHs(mol) - except: + mol = Chem.AddHs(mol) + except Exception: UtilFuncs.eprint("ERROR: ", smi) return [] @@ -701,14 +777,14 @@ # Initialize the output list output_smis = [] - state_to_charge = {"DEPROTONATED": [-1], - "PROTONATED": [0], - "BOTH": [-1, 0]} + state_to_charge = {"DEPROTONATED": [-1], "PROTONATED": [0], "BOTH": [-1, 0]} charges = state_to_charge[target_prot_state] # Now make the actual smiles match the target protonation state. - output_smis = ProtSubstructFuncs.set_protonation_charge(smis, idx, charges, prot_site_name) + output_smis = ProtSubstructFuncs.set_protonation_charge( + smis, idx, charges, prot_site_name + ) return output_smis @@ -759,11 +835,12 @@ atom.SetFormalCharge(charge) # Convert back to SMILE and add to output - out_smile = Chem.MolToSmiles(mol, isomericSmiles=True,canonical=True) + out_smile = Chem.MolToSmiles(mol, isomericSmiles=True, canonical=True) output.append(out_smile) return output + class ProtectUnprotectFuncs: """A namespace for storing functions that are useful for protecting and unprotecting molecules. To keep things organized. We need to identify and @@ -779,7 +856,7 @@ """ for atom in mol.GetAtoms(): - atom.SetProp('_protected', '0') + atom.SetProp("_protected", "0") @staticmethod def protect_molecule(mol, match): @@ -793,7 +870,7 @@ for idx in match: atom = mol.GetAtomWithIdx(idx) - atom.SetProp('_protected', '1') + atom.SetProp("_protected", "1") @staticmethod def get_unprotected_matches(mol, substruct): @@ -829,6 +906,7 @@ return False return True + class TestFuncs: """A namespace for storing functions that perform tests on the code. To keep things organized.""" @@ -839,53 +917,158 @@ smis = [ # [input smiles, pka, protonated, deprotonated, category] - ["C#CCO", "C#CCO", "C#CC[O-]", "Alcohol"], - ["C(=O)N", "NC=O", "[NH-]C=O", "Amide"], - ["CC(=O)NOC(C)=O", "CC(=O)NOC(C)=O", "CC(=O)[N-]OC(C)=O", "Amide_electronegative"], - ["COC(=N)N", "COC(N)=[NH2+]", "COC(=N)N", "AmidineGuanidine2"], - ["Brc1ccc(C2NCCS2)cc1", "Brc1ccc(C2[NH2+]CCS2)cc1", "Brc1ccc(C2NCCS2)cc1", "Amines_primary_secondary_tertiary"], - ["CC(=O)[n+]1ccc(N)cc1", "CC(=O)[n+]1ccc([NH3+])cc1", "CC(=O)[n+]1ccc(N)cc1", "Anilines_primary"], - ["CCNc1ccccc1", "CC[NH2+]c1ccccc1", "CCNc1ccccc1", "Anilines_secondary"], - ["Cc1ccccc1N(C)C", "Cc1ccccc1[NH+](C)C", "Cc1ccccc1N(C)C", "Anilines_tertiary"], - ["BrC1=CC2=C(C=C1)NC=C2", "Brc1ccc2[nH]ccc2c1", "Brc1ccc2[n-]ccc2c1", "Indole_pyrrole"], - ["O=c1cc[nH]cc1", "O=c1cc[nH]cc1", "O=c1cc[n-]cc1", "Aromatic_nitrogen_protonated"], - ["C-N=[N+]=[N@H]", "CN=[N+]=N", "CN=[N+]=[N-]", "Azide"], - ["BrC(C(O)=O)CBr", "O=C(O)C(Br)CBr", "O=C([O-])C(Br)CBr", "Carboxyl"], - ["NC(NN=O)=N", "NC(=[NH2+])NN=O", "N=C(N)NN=O", "AmidineGuanidine1"], - ["C(F)(F)(F)C(=O)NC(=O)C", "CC(=O)NC(=O)C(F)(F)F", "CC(=O)[N-]C(=O)C(F)(F)F", "Imide"], - ["O=C(C)NC(C)=O", "CC(=O)NC(C)=O", "CC(=O)[N-]C(C)=O", "Imide2"], - ["CC(C)(C)C(N(C)O)=O", "CN(O)C(=O)C(C)(C)C", "CN([O-])C(=O)C(C)(C)C", "N-hydroxyamide"], - ["C[N+](O)=O", "C[N+](=O)O", "C[N+](=O)[O-]", "Nitro"], - ["O=C1C=C(O)CC1", "O=C1C=C(O)CC1", "O=C1C=C([O-])CC1", "O=C-C=C-OH"], - ["C1CC1OO", "OOC1CC1", "[O-]OC1CC1", "Peroxide2"], - ["C(=O)OO", "O=COO", "O=CO[O-]", "Peroxide1"], - ["Brc1cc(O)cc(Br)c1", "Oc1cc(Br)cc(Br)c1", "[O-]c1cc(Br)cc(Br)c1", "Phenol"], - ["CC(=O)c1ccc(S)cc1", "CC(=O)c1ccc(S)cc1", "CC(=O)c1ccc([S-])cc1", "Phenyl_Thiol"], - ["C=CCOc1ccc(C(=O)O)cc1", "C=CCOc1ccc(C(=O)O)cc1", "C=CCOc1ccc(C(=O)[O-])cc1", "Phenyl_carboxyl"], - ["COP(=O)(O)OC", "COP(=O)(O)OC", "COP(=O)([O-])OC", "Phosphate_diester"], - ["CP(C)(=O)O", "CP(C)(=O)O", "CP(C)(=O)[O-]", "Phosphinic_acid"], - ["CC(C)OP(C)(=O)O", "CC(C)OP(C)(=O)O", "CC(C)OP(C)(=O)[O-]", "Phosphonate_ester"], - ["CC1(C)OC(=O)NC1=O", "CC1(C)OC(=O)NC1=O", "CC1(C)OC(=O)[N-]C1=O", "Ringed_imide1"], - ["O=C(N1)C=CC1=O", "O=C1C=CC(=O)N1", "O=C1C=CC(=O)[N-]1", "Ringed_imide2"], - ["O=S(OC)(O)=O", "COS(=O)(=O)O", "COS(=O)(=O)[O-]", "Sulfate"], - ["COc1ccc(S(=O)O)cc1", "COc1ccc(S(=O)O)cc1", "COc1ccc(S(=O)[O-])cc1", "Sulfinic_acid"], - ["CS(N)(=O)=O", "CS(N)(=O)=O", "CS([NH-])(=O)=O", "Sulfonamide"], - ["CC(=O)CSCCS(O)(=O)=O", "CC(=O)CSCCS(=O)(=O)O", "CC(=O)CSCCS(=O)(=O)[O-]", "Sulfonate"], - ["CC(=O)S", "CC(=O)S", "CC(=O)[S-]", "Thioic_acid"], - ["C(C)(C)(C)(S)", "CC(C)(C)S", "CC(C)(C)[S-]", "Thiol"], - ["Brc1cc[nH+]cc1", "Brc1cc[nH+]cc1", "Brc1ccncc1", "Aromatic_nitrogen_unprotonated"], - ["C=C(O)c1c(C)cc(C)cc1C", "C=C(O)c1c(C)cc(C)cc1C", "C=C([O-])c1c(C)cc(C)cc1C", "Vinyl_alcohol"], - ["CC(=O)ON", "CC(=O)O[NH3+]", "CC(=O)ON", "Primary_hydroxyl_amine"] + ["C#CCO", "C#CCO", "C#CC[O-]", "Alcohol"], + ["C(=O)N", "NC=O", "[NH-]C=O", "Amide"], + [ + "CC(=O)NOC(C)=O", + "CC(=O)NOC(C)=O", + "CC(=O)[N-]OC(C)=O", + "Amide_electronegative", + ], + ["COC(=N)N", "COC(N)=[NH2+]", "COC(=N)N", "AmidineGuanidine2"], + [ + "Brc1ccc(C2NCCS2)cc1", + "Brc1ccc(C2[NH2+]CCS2)cc1", + "Brc1ccc(C2NCCS2)cc1", + "Amines_primary_secondary_tertiary", + ], + [ + "CC(=O)[n+]1ccc(N)cc1", + "CC(=O)[n+]1ccc([NH3+])cc1", + "CC(=O)[n+]1ccc(N)cc1", + "Anilines_primary", + ], + ["CCNc1ccccc1", "CC[NH2+]c1ccccc1", "CCNc1ccccc1", "Anilines_secondary"], + [ + "Cc1ccccc1N(C)C", + "Cc1ccccc1[NH+](C)C", + "Cc1ccccc1N(C)C", + "Anilines_tertiary", + ], + [ + "BrC1=CC2=C(C=C1)NC=C2", + "Brc1ccc2[nH]ccc2c1", + "Brc1ccc2[n-]ccc2c1", + "Indole_pyrrole", + ], + [ + "O=c1cc[nH]cc1", + "O=c1cc[nH]cc1", + "O=c1cc[n-]cc1", + "Aromatic_nitrogen_protonated", + ], + ["C-N=[N+]=[N@H]", "CN=[N+]=N", "CN=[N+]=[N-]", "Azide"], + ["BrC(C(O)=O)CBr", "O=C(O)C(Br)CBr", "O=C([O-])C(Br)CBr", "Carboxyl"], + ["NC(NN=O)=N", "NC(=[NH2+])NN=O", "N=C(N)NN=O", "AmidineGuanidine1"], + [ + "C(F)(F)(F)C(=O)NC(=O)C", + "CC(=O)NC(=O)C(F)(F)F", + "CC(=O)[N-]C(=O)C(F)(F)F", + "Imide", + ], + ["O=C(C)NC(C)=O", "CC(=O)NC(C)=O", "CC(=O)[N-]C(C)=O", "Imide2"], + [ + "CC(C)(C)C(N(C)O)=O", + "CN(O)C(=O)C(C)(C)C", + "CN([O-])C(=O)C(C)(C)C", + "N-hydroxyamide", + ], + ["C[N+](O)=O", "C[N+](=O)O", "C[N+](=O)[O-]", "Nitro"], + ["O=C1C=C(O)CC1", "O=C1C=C(O)CC1", "O=C1C=C([O-])CC1", "O=C-C=C-OH"], + ["C1CC1OO", "OOC1CC1", "[O-]OC1CC1", "Peroxide2"], + ["C(=O)OO", "O=COO", "O=CO[O-]", "Peroxide1"], + [ + "Brc1cc(O)cc(Br)c1", + "Oc1cc(Br)cc(Br)c1", + "[O-]c1cc(Br)cc(Br)c1", + "Phenol", + ], + [ + "CC(=O)c1ccc(S)cc1", + "CC(=O)c1ccc(S)cc1", + "CC(=O)c1ccc([S-])cc1", + "Phenyl_Thiol", + ], + [ + "C=CCOc1ccc(C(=O)O)cc1", + "C=CCOc1ccc(C(=O)O)cc1", + "C=CCOc1ccc(C(=O)[O-])cc1", + "Phenyl_carboxyl", + ], + ["COP(=O)(O)OC", "COP(=O)(O)OC", "COP(=O)([O-])OC", "Phosphate_diester"], + ["CP(C)(=O)O", "CP(C)(=O)O", "CP(C)(=O)[O-]", "Phosphinic_acid"], + [ + "CC(C)OP(C)(=O)O", + "CC(C)OP(C)(=O)O", + "CC(C)OP(C)(=O)[O-]", + "Phosphonate_ester", + ], + [ + "CC1(C)OC(=O)NC1=O", + "CC1(C)OC(=O)NC1=O", + "CC1(C)OC(=O)[N-]C1=O", + "Ringed_imide1", + ], + ["O=C(N1)C=CC1=O", "O=C1C=CC(=O)N1", "O=C1C=CC(=O)[N-]1", "Ringed_imide2"], + ["O=S(OC)(O)=O", "COS(=O)(=O)O", "COS(=O)(=O)[O-]", "Sulfate"], + [ + "COc1ccc(S(=O)O)cc1", + "COc1ccc(S(=O)O)cc1", + "COc1ccc(S(=O)[O-])cc1", + "Sulfinic_acid", + ], + ["CS(N)(=O)=O", "CS(N)(=O)=O", "CS([NH-])(=O)=O", "Sulfonamide"], + [ + "CC(=O)CSCCS(O)(=O)=O", + "CC(=O)CSCCS(=O)(=O)O", + "CC(=O)CSCCS(=O)(=O)[O-]", + "Sulfonate", + ], + ["CC(=O)S", "CC(=O)S", "CC(=O)[S-]", "Thioic_acid"], + ["C(C)(C)(C)(S)", "CC(C)(C)S", "CC(C)(C)[S-]", "Thiol"], + [ + "Brc1cc[nH+]cc1", + "Brc1cc[nH+]cc1", + "Brc1ccncc1", + "Aromatic_nitrogen_unprotonated", + ], + [ + "C=C(O)c1c(C)cc(C)cc1C", + "C=C(O)c1c(C)cc(C)cc1C", + "C=C([O-])c1c(C)cc(C)cc1C", + "Vinyl_alcohol", + ], + ["CC(=O)ON", "CC(=O)O[NH3+]", "CC(=O)ON", "Primary_hydroxyl_amine"], ] smis_phos = [ - ["O=P(O)(O)OCCCC", "CCCCOP(=O)(O)O", "CCCCOP(=O)([O-])O", "CCCCOP(=O)([O-])[O-]", "Phosphate"], - ["CC(P(O)(O)=O)C", "CC(C)P(=O)(O)O", "CC(C)P(=O)([O-])O", "CC(C)P(=O)([O-])[O-]", "Phosphonate"] + [ + "O=P(O)(O)OCCCC", + "CCCCOP(=O)(O)O", + "CCCCOP(=O)([O-])O", + "CCCCOP(=O)([O-])[O-]", + "Phosphate", + ], + [ + "CC(P(O)(O)=O)C", + "CC(C)P(=O)(O)O", + "CC(C)P(=O)([O-])O", + "CC(C)P(=O)([O-])[O-]", + "Phosphonate", + ], ] # Load the average pKa values. - average_pkas = {l.split()[0].replace("*", ""):float(l.split()[3]) for l in open("site_substructures.smarts") if l.split()[0] not in ["Phosphate", "Phosphonate"]} - average_pkas_phos = {l.split()[0].replace("*", ""):[float(l.split()[3]), float(l.split()[6])] for l in open("site_substructures.smarts") if l.split()[0] in ["Phosphate", "Phosphonate"]} + average_pkas = { + l.split()[0].replace("*", ""): float(l.split()[3]) + for l in open("site_substructures.smarts") + if l.split()[0] not in ["Phosphate", "Phosphonate"] + } + average_pkas_phos = { + l.split()[0].replace("*", ""): [float(l.split()[3]), float(l.split()[6])] + for l in open("site_substructures.smarts") + if l.split()[0] in ["Phosphate", "Phosphonate"] + } print("Running Tests") print("=============") @@ -900,7 +1083,7 @@ "max_ph": -10000000, "pka_precision": 0.5, "smiles": "", - "label_states": True + "label_states": True, } for smi, protonated, deprotonated, category in smis: @@ -954,14 +1137,20 @@ args["min_ph"] = avg_pka args["max_ph"] = avg_pka - TestFuncs.test_check(args, [mix, deprotonated], ["DEPROTONATED", "DEPROTONATED"]) + TestFuncs.test_check( + args, [mix, deprotonated], ["DEPROTONATED", "DEPROTONATED"] + ) - avg_pka = 0.5 * (average_pkas_phos[category][0] + average_pkas_phos[category][1]) + avg_pka = 0.5 * ( + average_pkas_phos[category][0] + average_pkas_phos[category][1] + ) args["min_ph"] = avg_pka args["max_ph"] = avg_pka args["pka_precision"] = 5 # Should give all three - TestFuncs.test_check(args, [mix, deprotonated, protonated], ["BOTH", "BOTH"]) + TestFuncs.test_check( + args, [mix, deprotonated, protonated], ["BOTH", "BOTH"] + ) @staticmethod def test_check(args, expected_output, labels): @@ -981,28 +1170,56 @@ num_states = len(expected_output) - if (len(output) != num_states): - msg = args["smiles"] + " should have " + str(num_states) + \ - " states at at pH " + str(args["min_ph"]) + ": " + str(output) + if len(output) != num_states: + msg = ( + args["smiles"] + + " should have " + + str(num_states) + + " states at at pH " + + str(args["min_ph"]) + + ": " + + str(output) + ) print(msg) raise Exception(msg) - if (len(set([l[0] for l in output]) - set(expected_output)) != 0): - msg = args["smiles"] + " is not " + " AND ".join(expected_output) + \ - " at pH " + str(args["min_ph"]) + " - " + str(args["max_ph"]) + \ - "; it is " + " AND ".join([l[0] for l in output]) + if len(set([l[0] for l in output]) - set(expected_output)) != 0: + msg = ( + args["smiles"] + + " is not " + + " AND ".join(expected_output) + + " at pH " + + str(args["min_ph"]) + + " - " + + str(args["max_ph"]) + + "; it is " + + " AND ".join([l[0] for l in output]) + ) print(msg) raise Exception(msg) - if (len(set([l[1] for l in output]) - set(labels)) != 0): - msg = args["smiles"] + " not labeled as " + " AND ".join(labels) + \ - "; it is " + " AND ".join([l[1] for l in output]) + if len(set([l[1] for l in output]) - set(labels)) != 0: + msg = ( + args["smiles"] + + " not labeled as " + + " AND ".join(labels) + + "; it is " + + " AND ".join([l[1] for l in output]) + ) print(msg) raise Exception(msg) ph_range = sorted(list(set([args["min_ph"], args["max_ph"]]))) ph_range_str = "(" + " - ".join("{0:.2f}".format(n) for n in ph_range) + ")" - print("(CORRECT) " + ph_range_str.ljust(10) + " " + args["smiles"] + " => " + " AND ".join([l[0] for l in output])) + print( + "(CORRECT) " + + ph_range_str.ljust(10) + + " " + + args["smiles"] + + " => " + + " AND ".join([l[0] for l in output]) + ) + def run(**kwargs): """A helpful, importable function for those who want to call Dimorphite-DL @@ -1019,6 +1236,7 @@ # Run the main function with the specified arguments. main(kwargs) + def run_with_mol_list(mol_lst, **kwargs): """A helpful, importable function for those who want to call Dimorphite-DL from another Python script rather than the command line. Note that this @@ -1037,10 +1255,13 @@ # Do a quick check to make sure the user input makes sense. for bad_arg in ["smiles", "smiles_file", "output_file", "test"]: if bad_arg in kwargs: - msg = "You're using Dimorphite-DL's run_with_mol_list(mol_lst, " + \ - "**kwargs) function, but you also passed the \"" + \ - bad_arg + "\" argument. Did you mean to use the " + \ - "run(**kwargs) function instead?" + msg = ( + "You're using Dimorphite-DL's run_with_mol_list(mol_lst, " + + '**kwargs) function, but you also passed the "' + + bad_arg + + '" argument. Did you mean to use the ' + + "run(**kwargs) function instead?" + ) print(msg) raise Exception(msg) @@ -1076,9 +1297,15 @@ m.SetProp(prop, str(val)) mols.append(m) else: - UtilFuncs.eprint("WARNING: Could not process molecule with SMILES string " + s + " and properties " + str(props)) + UtilFuncs.eprint( + "WARNING: Could not process molecule with SMILES string " + + s + + " and properties " + + str(props) + ) return mols + if __name__ == "__main__": main()
--- /dev/null Thu Jan 01 00:00:00 1970 +0000 +++ b/rdconf.py Sat Dec 04 16:40:23 2021 +0000 @@ -0,0 +1,229 @@ +#!/usr/bin/python3 + +import gzip +import os +import sys +from optparse import OptionParser + +from rdkit.Chem import AllChem as Chem + +""" +This script was originally written by David Koes, University of Pittsburgh: +https://github.com/dkoes/rdkit-scripts/blob/master/rdconf.py +It is licensed under the MIT licence. + +Given a smiles file, generate 3D conformers in output sdf. +Energy minimizes and filters conformers to meet energy window and rms constraints. + +Some time ago I compared this to alternative conformer generators and +it was quite competitive (especially after RDKit's UFF implementation +added OOP terms). +""" + + +# convert smiles to sdf +def getRMS(mol, c1, c2): + rms = Chem.GetBestRMS(mol, mol, c1, c2) + return rms + + +parser = OptionParser(usage="Usage: %prog [options] <input>.smi <output>.sdf") +parser.add_option( + "--maxconfs", + dest="maxconfs", + action="store", + help="maximum number of conformers to generate per a molecule (default 20)", + default="20", + type="int", + metavar="CNT", +) +parser.add_option( + "--sample_multiplier", + dest="sample", + action="store", + help="sample N*maxconfs conformers and choose the maxconformers with lowest energy (default 1)", + default="1", + type="float", + metavar="N", +) +parser.add_option( + "--seed", + dest="seed", + action="store", + help="random seed (default 9162006)", + default="9162006", + type="int", + metavar="s", +) +parser.add_option( + "--rms_threshold", + dest="rms", + action="store", + help="filter based on rms (default 0.7)", + default="0.7", + type="float", + metavar="R", +) +parser.add_option( + "--energy_window", + dest="energy", + action="store", + help="filter based on energy difference with lowest energy conformer", + default="10", + type="float", + metavar="E", +) +parser.add_option( + "-v", + "--verbose", + dest="verbose", + action="store_true", + default=False, + help="verbose output", +) +parser.add_option( + "--mmff", + dest="mmff", + action="store_true", + default=False, + help="use MMFF forcefield instead of UFF", +) +parser.add_option( + "--nomin", + dest="nomin", + action="store_true", + default=False, + help="don't perform energy minimization (bad idea)", +) +parser.add_option( + "--etkdg", + dest="etkdg", + action="store_true", + default=False, + help="use new ETKDG knowledge-based method instead of distance geometry", +) + + +(options, args) = parser.parse_args() + +if len(args) < 2: + parser.error("Need input and output") + sys.exit(-1) + +input = args[0] +output = args[1] +smifile = open(input) +if options.verbose: + print("Generating a maximum of", options.maxconfs, "per a mol") + +if options.etkdg and not Chem.ETKDG: + print("ETKDB does not appear to be implemented. Please upgrade RDKit.") + sys.exit(1) + +split = os.path.splitext(output) +if split[1] == ".gz": + outf = gzip.open(output, "wt+") + output = split[0] # strip .gz +else: + outf = open(output, "w+") + + +if os.path.splitext(output)[1] == ".pdb": + sdwriter = Chem.PDBWriter(outf) +else: + sdwriter = Chem.SDWriter(outf) + +if sdwriter is None: + print("Could not open ".output) + sys.exit(-1) + +for line in smifile: + toks = line.split() + smi = toks[0] + name = " ".join(toks[1:]) + + pieces = smi.split(".") + if len(pieces) > 1: + smi = max(pieces, key=len) # take largest component by length + print("Taking largest component: %s\t%s" % (smi, name)) + + mol = Chem.MolFromSmiles(smi) + if mol is not None: + if options.verbose: + print(smi) + try: + Chem.SanitizeMol(mol) + mol = Chem.AddHs(mol) + mol.SetProp("_Name", name) + + if options.etkdg: + cids = Chem.EmbedMultipleConfs( + mol, int(options.sample * options.maxconfs), Chem.ETKDG() + ) + else: + cids = Chem.EmbedMultipleConfs( + mol, int(options.sample * options.maxconfs), randomSeed=options.seed + ) + if options.verbose: + print(len(cids), "conformers found") + cenergy = [] + for conf in cids: + # not passing confID only minimizes the first conformer + if options.nomin: + cenergy.append(conf) + elif options.mmff: + converged = Chem.MMFFOptimizeMolecule(mol, confId=conf) + mp = Chem.MMFFGetMoleculeProperties(mol) + cenergy.append( + Chem.MMFFGetMoleculeForceField( + mol, mp, confId=conf + ).CalcEnergy() + ) + else: + converged = not Chem.UFFOptimizeMolecule(mol, confId=conf) + cenergy.append( + Chem.UFFGetMoleculeForceField(mol, confId=conf).CalcEnergy() + ) + if options.verbose: + print("Convergence of conformer", conf, converged) + + mol = Chem.RemoveHs(mol) + sortedcids = sorted(cids, key=lambda cid: cenergy[cid]) + if len(sortedcids) > 0: + mine = cenergy[sortedcids[0]] + else: + mine = 0 + if options.rms == 0: + cnt = 0 + for conf in sortedcids: + if cnt >= options.maxconfs: + break + if (options.energy < 0) or cenergy[conf] - mine <= options.energy: + sdwriter.write(mol, conf) + cnt += 1 + else: + written = {} + for conf in sortedcids: + if len(written) >= options.maxconfs: + break + # check rmsd + passed = True + for seenconf in written.keys(): + rms = getRMS(mol, seenconf, conf) + if (rms < options.rms) or ( + options.energy > 0 and cenergy[conf] - mine > options.energy + ): + passed = False + break + if passed: + written[conf] = True + sdwriter.write(mol, conf) + except (KeyboardInterrupt, SystemExit): + raise + except Exception as e: + print("Exception", e) + else: + print("ERROR:", smi) + +sdwriter.close() +outf.close()
--- a/rdkit_descriptors.py Wed Feb 17 12:59:24 2021 +0000 +++ b/rdkit_descriptors.py Sat Dec 04 16:40:23 2021 +0000 @@ -8,7 +8,7 @@ from rdkit.Chem import Descriptors -def get_supplier(infile, format='smiles'): +def get_supplier(infile, format="smiles"): """ Returns a generator over a SMILES or InChI file. Every element is of RDKit molecule and has its original string as _Name property. @@ -16,14 +16,20 @@ with open(infile) as handle: for line in handle: line = line.strip() - if format == 'smiles': + if format == "smiles": mol = Chem.MolFromSmiles(line, sanitize=True) - elif format == 'inchi': - mol = Chem.inchi.MolFromInchi(line, sanitize=True, removeHs=True, logLevel=None, treatWarningAsError=False) + elif format == "inchi": + mol = Chem.inchi.MolFromInchi( + line, + sanitize=True, + removeHs=True, + logLevel=None, + treatWarningAsError=False, + ) if mol is None: yield False else: - mol.SetProp('_Name', line.split('\t')[0]) + mol.SetProp("_Name", line.split("\t")[0]) yield mol @@ -31,9 +37,13 @@ """ Returns all descriptor functions under the Chem.Descriptors Module as tuple of (name, function) """ - ret = [(name, f) for name, f in inspect.getmembers(Descriptors) if inspect.isfunction(f) and not name.startswith('_')] + ret = [ + (name, f) + for name, f in inspect.getmembers(Descriptors) + if inspect.isfunction(f) and not name.startswith("_") + ] # some which are not in the official Descriptors module we need to add manually - ret.extend([('FormalCharge', Chem.GetFormalCharge), ('SSSR', Chem.GetSSSR)]) + ret.extend([("FormalCharge", Chem.GetFormalCharge), ("SSSR", Chem.GetSSSR)]) ret.sort() return ret @@ -48,40 +58,54 @@ if __name__ == "__main__": parser = argparse.ArgumentParser() - parser.add_argument('-i', '--infile', required=True, help='Path to the input file.') + parser.add_argument("-i", "--infile", required=True, help="Path to the input file.") parser.add_argument("--iformat", help="Specify the input file format.") - parser.add_argument('-o', '--outfile', type=argparse.FileType('w+'), - default=sys.stdout, - help="path to the result file, default is stdout") + parser.add_argument( + "-o", + "--outfile", + type=argparse.FileType("w+"), + default=sys.stdout, + help="path to the result file, default is stdout", + ) - parser.add_argument('-s', '--select', default=None, - help="select a subset of comma-separated descriptors to use") + parser.add_argument( + "-s", + "--select", + default=None, + help="select a subset of comma-separated descriptors to use", + ) - parser.add_argument("--header", dest="header", action="store_true", - default=False, - help="Write header line.") + parser.add_argument( + "--header", + dest="header", + action="store_true", + default=False, + help="Write header line.", + ) args = parser.parse_args() - if args.iformat == 'sdf': + if args.iformat == "sdf": supplier = Chem.SDMolSupplier(args.infile) - elif args.iformat == 'smi': - supplier = get_supplier(args.infile, format='smiles') - elif args.iformat == 'inchi': - supplier = get_supplier(args.infile, format='inchi') - elif args.iformat == 'pdb': + elif args.iformat == "smi": + supplier = get_supplier(args.infile, format="smiles") + elif args.iformat == "inchi": + supplier = get_supplier(args.infile, format="inchi") + elif args.iformat == "pdb": supplier = [Chem.MolFromPDBFile(args.infile)] - elif args.iformat == 'mol2': + elif args.iformat == "mol2": supplier = [Chem.MolFromMol2File(args.infile)] functions = get_rdkit_descriptor_functions() - if args.select and args.select != 'None': - selected = args.select.split(',') + if args.select and args.select != "None": + selected = args.select.split(",") functions = [(name, f) for name, f in functions if name in selected] if args.header: - args.outfile.write('%s\n' % '\t'.join(['MoleculeID'] + [name for name, f in functions])) + args.outfile.write( + "%s\n" % "\t".join(["MoleculeID"] + [name for name, f in functions]) + ) for mol in supplier: if not mol: @@ -91,4 +115,7 @@ molecule_id = mol.GetProp("_Name") except KeyError: molecule_id = Chem.MolToSmiles(mol) - args.outfile.write("%s\n" % '\t'.join([molecule_id] + [str(round(res, 6)) for name, res in descs])) + args.outfile.write( + "%s\n" + % "\t".join([molecule_id] + [str(round(res, 6)) for name, res in descs]) + )
--- a/sdf_to_tab.py Wed Feb 17 12:59:24 2021 +0000 +++ b/sdf_to_tab.py Sat Dec 04 16:40:23 2021 +0000 @@ -13,36 +13,55 @@ if mols[n]: d = mols[n].GetPropsAsDict() # filter dict for desired props - if vars.props.strip() == '': # none specified, return all - d = {prop: val for (prop, val) in d.items() if not any(x in str(val) for x in ['\n', '\t'])} # remove items containing newlines or tabs + if vars.props.strip() == "": # none specified, return all + d = { + prop: val + for (prop, val) in d.items() + if not any(x in str(val) for x in ["\n", "\t"]) + } # remove items containing newlines or tabs else: - d = {prop: val for (prop, val) in d.items() if prop in vars.props.replace(' ', '').split(',')} # remove items not requested via CLI + d = { + prop: val + for (prop, val) in d.items() + if prop in vars.props.replace(" ", "").split(",") + } # remove items not requested via CLI if vars.name: - d['SDFMoleculeName'] = mols[n].GetProp('_Name') + d["SDFMoleculeName"] = mols[n].GetProp("_Name") if vars.smiles: - d['SMILES'] = Chem.MolToSmiles(mols[n], isomericSmiles=False) - d['Index'] = int(n) + d["SMILES"] = Chem.MolToSmiles(mols[n], isomericSmiles=False) + d["Index"] = int(n) df = df.append(d, ignore_index=True) else: print("Molecule could not be read - skipped.") - df = df.astype({'Index': int}).set_index('Index') + df = df.astype({"Index": int}).set_index("Index") sorted_cols = sorted(df.columns.values.tolist()) - df.to_csv(vars.out, sep='\t', header=vars.header, columns=sorted_cols) + df.to_csv(vars.out, sep="\t", header=vars.header, columns=sorted_cols) def main(): parser = argparse.ArgumentParser(description="Convert SDF to tabular") - parser.add_argument('--inp', '-i', help="The input file", required=True) - parser.add_argument('--out', '-o', help="The output file", required=True) - parser.add_argument('--props', '-p', help="Properties to filter (leave blank for all)", required=True) - parser.add_argument('--header', '-t', action='store_true', - help="Write property name as the first row.") - parser.add_argument('--smiles', '-s', action='store_true', - help="Include SMILES in output.") - parser.add_argument('--name', '-n', action='store_true', - help="Include molecule name in output.") + parser.add_argument("--inp", "-i", help="The input file", required=True) + parser.add_argument("--out", "-o", help="The output file", required=True) + parser.add_argument( + "--props", + "-p", + help="Properties to filter (leave blank for all)", + required=True, + ) + parser.add_argument( + "--header", + "-t", + action="store_true", + help="Write property name as the first row.", + ) + parser.add_argument( + "--smiles", "-s", action="store_true", help="Include SMILES in output." + ) + parser.add_argument( + "--name", "-n", action="store_true", help="Include molecule name in output." + ) sdf_to_tab(parser.parse_args())
--- /dev/null Thu Jan 01 00:00:00 1970 +0000 +++ b/test-data/rdconf_output.sdf Sat Dec 04 16:40:23 2021 +0000 @@ -0,0 +1,166 @@ +staurosporine + RDKit 3D + + 35 42 0 0 0 0 0 0 0 0999 V2000 + -2.1656 1.4438 -2.0402 C 0 0 0 0 0 0 0 0 0 0 0 0 + -1.5064 0.5224 -1.0006 C 0 0 1 0 0 0 0 0 0 0 0 0 + -2.5333 0.2902 0.0771 C 0 0 1 0 0 0 0 0 0 0 0 0 + -3.0448 -1.1355 -0.1222 C 0 0 1 0 0 0 0 0 0 0 0 0 + -1.8499 -2.0325 0.1086 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.9248 -1.7530 -1.0664 C 0 0 1 0 0 0 0 0 0 0 0 0 + -1.2333 -0.6270 -1.7456 O 0 0 0 0 0 0 0 0 0 0 0 0 + 0.4794 -1.8256 -0.6986 N 0 0 0 0 0 0 0 0 0 0 0 0 + 1.2443 -2.8970 -0.6134 C 0 0 0 0 0 0 0 0 0 0 0 0 + 0.9172 -4.2121 -0.8557 C 0 0 0 0 0 0 0 0 0 0 0 0 + 1.8835 -5.2113 -0.7023 C 0 0 0 0 0 0 0 0 0 0 0 0 + 3.1496 -4.8403 -0.3079 C 0 0 0 0 0 0 0 0 0 0 0 0 + 3.4981 -3.5086 -0.0573 C 0 0 0 0 0 0 0 0 0 0 0 0 + 2.5336 -2.5530 -0.2153 C 0 0 0 0 0 0 0 0 0 0 0 0 + 2.5282 -1.1902 -0.0555 C 0 0 0 0 0 0 0 0 0 0 0 0 + 3.4701 -0.2506 0.3363 C 0 0 0 0 0 0 0 0 0 0 0 0 + 3.1276 1.0747 0.4177 C 0 0 0 0 0 0 0 0 0 0 0 0 + 1.8462 1.4665 0.1077 C 0 0 0 0 0 0 0 0 0 0 0 0 + 1.2026 2.7102 0.1107 C 0 0 0 0 0 0 0 0 0 0 0 0 + 1.7041 3.9456 0.4421 C 0 0 0 0 0 0 0 0 0 0 0 0 + 0.8338 5.0265 0.3768 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.4727 4.8205 -0.0097 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.9490 3.5396 -0.3412 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.0910 2.4739 -0.2786 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.2989 1.1681 -0.5288 N 0 0 0 0 0 0 0 0 0 0 0 0 + 0.9108 0.5646 -0.2791 C 0 0 0 0 0 0 0 0 0 0 0 0 + 1.2388 -0.7709 -0.3642 C 0 0 0 0 0 0 0 0 0 0 0 0 + 4.2788 1.9083 0.8642 C 0 0 0 0 0 0 0 0 0 0 0 0 + 5.3369 0.9521 1.0170 N 0 0 0 0 0 0 0 0 0 0 0 0 + 4.8631 -0.3694 0.7084 C 0 0 0 0 0 0 0 0 0 0 0 0 + 5.6279 -1.3464 0.7907 O 0 0 0 0 0 0 0 0 0 0 0 0 + -4.1928 -1.4531 0.6537 N 0 0 0 0 0 0 0 0 0 0 0 0 + -5.2852 -0.5939 0.2385 C 0 0 0 0 0 0 0 0 0 0 0 0 + -1.8857 0.2845 1.3121 O 0 0 0 0 0 0 0 0 0 0 0 0 + -2.4801 1.0939 2.2570 C 0 0 0 0 0 0 0 0 0 0 0 0 + 2 1 1 6 + 2 3 1 0 + 3 4 1 0 + 4 5 1 0 + 6 5 1 1 + 6 7 1 0 + 6 8 1 0 + 8 9 1 0 + 9 10 2 0 + 10 11 1 0 + 11 12 2 0 + 12 13 1 0 + 13 14 2 0 + 14 15 1 0 + 15 16 2 0 + 16 17 1 0 + 17 18 2 0 + 18 19 1 0 + 19 20 2 0 + 20 21 1 0 + 21 22 2 0 + 22 23 1 0 + 23 24 2 0 + 24 25 1 0 + 25 26 1 0 + 26 27 2 0 + 17 28 1 0 + 28 29 1 0 + 29 30 1 0 + 30 31 2 0 + 4 32 1 1 + 32 33 1 0 + 3 34 1 1 + 34 35 1 0 + 7 2 1 0 + 25 2 1 0 + 27 8 1 0 + 14 9 1 0 + 27 15 1 0 + 30 16 1 0 + 26 18 1 0 + 24 19 1 0 +M END +$$$$ +staurosporine + RDKit 3D + + 35 42 0 0 0 0 0 0 0 0999 V2000 + -2.3068 0.9355 -2.4621 C 0 0 0 0 0 0 0 0 0 0 0 0 + -1.6484 0.1936 -1.2955 C 0 0 1 0 0 0 0 0 0 0 0 0 + -2.6628 -0.4491 -0.4739 C 0 0 1 0 0 0 0 0 0 0 0 0 + -2.1102 -1.3841 0.5829 C 0 0 1 0 0 0 0 0 0 0 0 0 + -1.3580 -2.4343 -0.1341 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.6301 -1.9615 -1.3703 C 0 0 1 0 0 0 0 0 0 0 0 0 + -1.0034 -0.8456 -1.9685 O 0 0 0 0 0 0 0 0 0 0 0 0 + 0.7323 -1.7671 -0.8854 N 0 0 0 0 0 0 0 0 0 0 0 0 + 1.6653 -2.7175 -0.8097 C 0 0 0 0 0 0 0 0 0 0 0 0 + 1.6030 -4.0416 -1.1929 C 0 0 0 0 0 0 0 0 0 0 0 0 + 2.7336 -4.8209 -0.9993 C 0 0 0 0 0 0 0 0 0 0 0 0 + 3.8672 -4.2655 -0.4408 C 0 0 0 0 0 0 0 0 0 0 0 0 + 3.9097 -2.9234 -0.0599 C 0 0 0 0 0 0 0 0 0 0 0 0 + 2.7941 -2.1557 -0.2513 C 0 0 0 0 0 0 0 0 0 0 0 0 + 2.5524 -0.8186 0.0257 C 0 0 0 0 0 0 0 0 0 0 0 0 + 3.2591 0.2074 0.5765 C 0 0 0 0 0 0 0 0 0 0 0 0 + 2.6138 1.4431 0.6965 C 0 0 0 0 0 0 0 0 0 0 0 0 + 1.3053 1.6277 0.2726 C 0 0 0 0 0 0 0 0 0 0 0 0 + 0.4639 2.7123 0.2701 C 0 0 0 0 0 0 0 0 0 0 0 0 + 0.6421 4.0028 0.7116 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.3869 4.9173 0.5986 C 0 0 0 0 0 0 0 0 0 0 0 0 + -1.5824 4.5165 0.0416 C 0 0 0 0 0 0 0 0 0 0 0 0 + -1.7175 3.2124 -0.3878 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.7245 2.2626 -0.2991 C 0 0 0 0 0 0 0 0 0 0 0 0 + -0.6365 0.9796 -0.6340 N 0 0 0 0 0 0 0 0 0 0 0 0 + 0.6078 0.6133 -0.2727 C 0 0 0 0 0 0 0 0 0 0 0 0 + 1.2251 -0.6244 -0.3999 C 0 0 0 0 0 0 0 0 0 0 0 0 + 3.5496 2.4028 1.3130 C 0 0 0 0 0 0 0 0 0 0 0 0 + 4.7624 1.6652 1.5409 N 0 0 0 0 0 0 0 0 0 0 0 0 + 4.5952 0.3088 1.0910 C 0 0 0 0 0 0 0 0 0 0 0 0 + 5.5219 -0.5061 1.1939 O 0 0 0 0 0 0 0 0 0 0 0 0 + -1.3679 -0.6619 1.5643 N 0 0 0 0 0 0 0 0 0 0 0 0 + -2.2073 0.2673 2.2885 C 0 0 0 0 0 0 0 0 0 0 0 0 + -3.6735 0.2555 0.0846 O 0 0 0 0 0 0 0 0 0 0 0 0 + -4.9519 -0.0773 -0.2685 C 0 0 0 0 0 0 0 0 0 0 0 0 + 2 1 1 6 + 2 3 1 0 + 3 4 1 0 + 4 5 1 0 + 6 5 1 1 + 6 7 1 0 + 6 8 1 0 + 8 9 1 0 + 9 10 2 0 + 10 11 1 0 + 11 12 2 0 + 12 13 1 0 + 13 14 2 0 + 14 15 1 0 + 15 16 2 0 + 16 17 1 0 + 17 18 2 0 + 18 19 1 0 + 19 20 2 0 + 20 21 1 0 + 21 22 2 0 + 22 23 1 0 + 23 24 2 0 + 24 25 1 0 + 25 26 1 0 + 26 27 2 0 + 17 28 1 0 + 28 29 1 0 + 29 30 1 0 + 30 31 2 0 + 4 32 1 1 + 32 33 1 0 + 3 34 1 1 + 34 35 1 0 + 7 2 1 0 + 25 2 1 0 + 27 8 1 0 + 14 9 1 0 + 27 15 1 0 + 30 16 1 0 + 26 18 1 0 + 24 19 1 0 +M END +$$$$