comparison tools/rdock/bin/sdtether @ 3:b02d74d22d05 draft default tip

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3:b02d74d22d05

#! /usr/bin/env python
#
# Substitute for rbtether of rDock. Will align input molecules to a reference fragment defined by a smarts string, 
# it will add a TETHERED ATOM property field to the output SDF that is correctly understood by rDock 
# rDock will restrain the matching atom positions to the reference molecule coordinates.
#
# Initially implemented with a conformational search algorithm to better match target coordinates.
# But had problems with OBabel FF generating non-sense conformers. So in this version the conformer search is commented out.
# Now if the input molecule do not have a good conformation, might not align well with the target. This effect will be 
# dimished or even vanish if the SMARTS string is defined for a rigid region (like a ring).
# I'm still trying to incorporate somehow this conformational search.
#
# Script distributed under GNU LGPL 3.0 along rDock software.
# 
# Author: Daniel Alvarez-Garcia
# Date: 08-11-2013

import math
import pybel
import numpy as npy

def superpose3D(ref, target, weights=None,refmask=None,targetmask=None,returnRotMat=False):
    """superpose3D performs 3d superposition using a weighted Kabsch algorithm : http://dx.doi.org/10.1107%2FS0567739476001873 & doi: 10.1529/biophysj.105.066654
    definition : superpose3D(ref, target, weights,refmask,targetmask)
    @parameter 1 :  ref - xyz coordinates of the reference structure (the ligand for instance)
    @type 1 :       float64 numpy array (nx3)
    ---
    @parameter 2 :  target - theoretical target positions to which we should move (does not need to be physically relevant.
    @type 2 :       float 64 numpy array (nx3)
    ---
    @parameter 3:   weights - numpy array of atom weights (usuallly between 0 and 1)
    @type 3 :       float 64 numpy array (n)
    @parameter 4:   mask - a numpy boolean mask for designating atoms to include
    Note ref and target positions must have the same dimensions -> n*3 numpy arrays where n is the number of points (or atoms)
    Returns a set of new coordinates, aligned to the target state as well as the rmsd
    """
    if weights == None :
        weights=1.0
    if refmask == None :
        refmask=npy.ones(len(ref),"bool")
    if targetmask == None :
        targetmask=npy.ones(len(target),"bool")
    #first get the centroid of both states
    ref_centroid = npy.mean(ref[refmask]*weights,axis=0)
    #print ref_centroid
    refCenteredCoords=ref-ref_centroid
    #print refCenteredCoords
    target_centroid=npy.mean(target[targetmask]*weights,axis=0)
    targetCenteredCoords=target-target_centroid
    #print targetCenteredCoords
    #the following steps come from : http://www.pymolwiki.org/index.php/OptAlign#The_Code and http://en.wikipedia.org/wiki/Kabsch_algorithm
    # Initial residual, see Kabsch.
    E0 = npy.sum( npy.sum(refCenteredCoords[refmask] * refCenteredCoords[refmask]*weights,axis=0),axis=0) + npy.sum( npy.sum(targetCenteredCoords[targetmask] * targetCenteredCoords[targetmask]*weights,axis=0),axis=0)
    reftmp=npy.copy(refCenteredCoords[refmask])
    targettmp=npy.copy(targetCenteredCoords[targetmask])
    #print refCenteredCoords[refmask]
    #single value decomposition of the dotProduct of both position vectors
    try:
        dotProd = npy.dot( npy.transpose(reftmp), targettmp* weights)
        V, S, Wt = npy.linalg.svd(dotProd )
    except Exception:
        try:
            dotProd = npy.dot( npy.transpose(reftmp), targettmp)
            V, S, Wt = npy.linalg.svd(dotProd )
        except Exception:
            print >> sys.stderr,"Couldn't perform the Single Value Decomposition, skipping alignment"
        return ref, 0
    # we already have our solution, in the results from SVD.
    # we just need to check for reflections and then produce
    # the rotation.  V and Wt are orthonormal, so their det's
    # are +/-1.
    reflect = float(str(float(npy.linalg.det(V) * npy.linalg.det(Wt))))
    if reflect == -1.0:
        S[-1] = -S[-1]
        V[:,-1] = -V[:,-1]
    rmsd = E0 - (2.0 * sum(S))
    rmsd = npy.sqrt(abs(rmsd / len(ref[refmask])))   #get the rmsd
    #U is simply V*Wt
    U = npy.dot(V, Wt)  #get the rotation matrix
    # rotate and translate the molecule
    new_coords = npy.dot((refCenteredCoords), U)+ target_centroid  #translate & rotate
    #new_coords=(refCenteredCoords + target_centroid)
    #print U
    if returnRotMat : 
        return U, ref_centroid, target_centroid, rmsd
    return new_coords,rmsd


def squared_distance(coordsA, coordsB):
    """Find the squared distance between two 3-tuples"""
    sqrdist = sum( (a-b)**2 for a, b in zip(coordsA, coordsB) )
    return sqrdist
    
def rmsd(allcoordsA, allcoordsB):
    """Find the RMSD between two lists of 3-tuples"""
    deviation = sum(squared_distance(atomA, atomB) for
                    (atomA, atomB) in zip(allcoordsA, allcoordsB))
    return math.sqrt(deviation / float(len(allcoordsA)))
    
def mapToCrystal(xtal, pose):
    """Some docking programs might alter the order of the atoms in the output (like Autodock Vina does...)
     this will mess up the rmsd calculation with OpenBabel"""
    query = pybel.ob.CompileMoleculeQuery(xtal.OBMol) 
    mapper=pybel.ob.OBIsomorphismMapper.GetInstance(query)
    mappingpose = pybel.ob.vvpairUIntUInt()
    exit=mapper.MapUnique(pose.OBMol,mappingpose)
    return mappingpose[0]

def takeCoords(obmol):
    """Take coordinates of an OBMol as a npy array"""
    return npy.array([atom.coords for atom in obmol])

def updateCoords(obmol, newcoords):
    "Update OBMol coordinates. newcoords is a numpy array"
    for i,atom in enumerate(obmol):
        atom.OBAtom.SetVector(*newcoords[i])

def prepareAtomString(idlist):
    s = ""
    n = len(idlist)
    for i, id in enumerate(idlist):
        s += "%i"%id
        if (i+1) == n: s+="\n"
        elif (i+1)%35 == 0: s+=",\n"
        else: s+=","
    return s


if __name__ == "__main__":
    import sys
    
    if len(sys.argv) != 5:
        sys.exit("USAGE: %s reference.sdf input.sdf output.sdf 'SMARTS'"%sys.argv[0])
    
    refsdf = sys.argv[1]
    molsdf = sys.argv[2]
    outsdf = sys.argv[3]
    smarts = pybel.Smarts(sys.argv[4])

    # Read reference pose and get atom list matching smarts query
    # if more than 1 match, take the first one
    ref = next(pybel.readfile("sdf", refsdf))
    refMatchIds = smarts.findall(ref)
    numRefMatchs = len(refMatchIds)

    if not numRefMatchs:
	sys.exit("No match found in the reference structure and the SMARTS string given. Please check it.")

    if numRefMatchs > 1: 
	print "More than one match in the reference molecule for the SMARTS string given. Will tether each input molecule all possible ways."

    refIndxPerMatch = [npy.array(rmi) - 1 for rmi in refMatchIds]

    # Take coordinates for the reference matched atoms
    refCoords = takeCoords(ref)
    refMatchCoords = [npy.take(refCoords, refIndx, axis=0) for refIndx in refIndxPerMatch]

    # Do the same for molecule in molsdf
    out=pybel.Outputfile('sdf', outsdf, overwrite=True)
    molSupp = pybel.readfile("sdf", molsdf)
    ff = pybel.ob.OBForceField_FindForceField('MMFF94')
    for i,mol in enumerate(molSupp):
	print "## Molecule %i"%(i+1),
	mol.OBMol.DeleteNonPolarHydrogens()
   	molMatchAllIds = smarts.findall(mol)
	numMatchs = len(molMatchAllIds)
	
	if numMatchs == 0:
		print "No_Match",
		continue
	elif numMatchs ==1:
		print "Match", 
	elif numMatchs > 1: 
                print "Multiple_Match SMART Matches for this molecule (%d)"%numMatchs,

	# If more than one match, write an output of the same molecule for each match
	# Start a default bestcoord and rmsd for later looping for each pose
	bestCoordPerMatch = [[0 for i in range(numMatchs)] for i in range(numRefMatchs)]
	bestRMSPerMatch = [[999 for i in range(numMatchs)] for i in range(numRefMatchs)]	

        # Will do a randomrotorsearch to find conformer with the lower rmsd when superposing
        # At least 20 when possible
        #ff.Setup(mol.OBMol)
	#numats = mol.OBMol.NumAtoms()
	#numrot = mol.OBMol.NumRotors()
	#print "Atoms: %i, Rotors: %i"%(numats, numrot)
	#geomopt = 300
	#genconf = 100
	# increase iterations if bigger molecule or bigger number of rotatable bonds
	# for allowing better sampling
	#if numats > 40 and numrot > 5: 
	#	geomopt = 300
	#	genconf = 150
	#if numats > 55 and numrot > 7: 
	#	genconf = 100
	#	geomopt = 500
        #print "\tDoing conformational search with WeightedRotorSearch (%i, %i)..."%(genconf, geomopt),
	#ff.SteepestDescent(500, 1.0e-4)
        #ff.WeightedRotorSearch(genconf,geomopt)
	#ff.ConjugateGradients(500, 1.0e-6)
	#ff.GetConformers(mol.OBMol)
	#numconf = mol.OBMol.NumConformers()
	numconf = 1
	#print "%i conformers generated"%numconf
        if numconf > 1:
            # Doing conf search
            #for i in range(numconf):
            #    mol.OBMol.SetConformer(i)
            #    confCoords = takeCoords(mol)
	    # 	print 'coord:',confCoords[0,:]
            #    
            #    for imatch, molMatchIds in enumerate(molMatchAllIds):
            #        molMatchIndx = npy.array(molMatchIds) - 1
            #        confMatchCoords = npy.take(confCoords, molMatchIndx, axis=0)
            #        
            #        # Align: Get rotation matrix between the two sets of coords
            #        # Apply rotation to the whole target molecule
            #        rotMat, targetCentroid, refCentroid, rmsd = superpose3D(confMatchCoords, refMatchCoords, returnRotMat=True)
            #        if rmsd < bestRMSPerMatch[imatch]: 
            #            newcoords = npy.dot((confCoords - targetCentroid), rotMat) + refCentroid
            #            bestRMSPerMatch[imatch] = rmsd
            #            bestCoordPerMatch[imatch] = newcoords
	    #	#if bestrms < 0.01: break
       	    pass 
        else:
            molCoords = takeCoords(mol)
            for imatch, molMatchIds in enumerate(molMatchAllIds):
		    # loop in each matching way for the input molecule
                    molMatchIndx = npy.array(molMatchIds) - 1
                    molMatchCoords = npy.take(molCoords, molMatchIndx, axis=0)
                    
		    # Loop over the reference matches
                    # Align: Get rotation matrix between the two sets of coords
                    # Apply rotation to the whole target molecule
		    for ir, refMatchCoord in enumerate(refMatchCoords):
                    	rotMat, targetCentroid, refCentroid, rmsd = superpose3D(molMatchCoords, refMatchCoord, returnRotMat=True)
                    	if rmsd < bestRMSPerMatch[ir][imatch]:
                        	newcoords = npy.dot((molCoords - targetCentroid), rotMat) + refCentroid
                        	bestRMSPerMatch[ir][imatch] = rmsd
                        	bestCoordPerMatch[ir][imatch] = newcoords
            
        # Finally update molecule coordinates with the best matching coordinates found
	# change molecule coordinates, set TETHERED ATOMS property and save
	for imatch in range(numMatchs):
		for irefmatch in range(numRefMatchs):
			bestCoord = bestCoordPerMatch[irefmatch][imatch]
			bestRMS = bestRMSPerMatch[irefmatch][imatch]
        		print "\tBest RMSD reached (match %d, refmatch %d): %s"%(imatch, irefmatch, bestRMS)
			molMatchID = molMatchAllIds[imatch]
        		updateCoords(mol, bestCoord)
        		newData = pybel.ob.OBPairData()
        		newData.SetAttribute("TETHERED ATOMS")
        		newData.SetValue(prepareAtomString(molMatchID))

			mol.OBMol.DeleteData("TETHERED ATOMS") # Remove Previous DATA
        		mol.OBMol.CloneData(newData)	       # Add new data
        		out.write(mol)
    
    out.close()
   
    print "DONE"
    sys.stdout.close()
    sys.stderr.close()