rdkit-data 201309-1 / usr / share / RDKit / Contrib / mmpa / rfrag.py

# Copyright (c) 2013, GlaxoSmithKline Research & Development Ltd.
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#       products derived from this software without specific prior written
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# LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
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# Created by Jameed Hussain, July 2013

import sys
import re
from rdkit import Chem

def find_correct(f_array):

    core = ""
    side_chains = ""

    for f in f_array:
        attachments = f.count("*")
        if (attachments == 1):
            side_chains = "%s.%s" % (side_chains,f)
        else:
            core = f

    side_chains = side_chains.lstrip('.')

    #cansmi the side chains
    temp = Chem.MolFromSmiles(side_chains)
    side_chains = Chem.MolToSmiles( temp, isomericSmiles=True )

    #and cansmi the core
    temp = Chem.MolFromSmiles(core)
    core = Chem.MolToSmiles( temp, isomericSmiles=True )

    return core,side_chains

def delete_bonds(smi,id,mol,bonds,out):

    #use the same parent mol object and create editable mol
    em = Chem.EditableMol(mol)

    #loop through the bonds to delete
    isotope = 0
    isotope_track = {};
    for i in bonds:
        isotope += 1
        #remove the bond
        em.RemoveBond(i[0],i[1])

        #now add attachement points
        newAtomA = em.AddAtom(Chem.Atom(0))
        em.AddBond(i[0],newAtomA,Chem.BondType.SINGLE)

        newAtomB = em.AddAtom(Chem.Atom(0))
        em.AddBond(i[1],newAtomB,Chem.BondType.SINGLE)

        #keep track of where to put isotopes
        isotope_track[newAtomA] = isotope
        isotope_track[newAtomB] = isotope


    #should be able to get away without sanitising mol
    #as the existing valencies/atoms not changed
    modifiedMol = em.GetMol()

    #canonical smiles can be different with and without the isotopes
    #hence to keep track of duplicates use fragmented_smi_noIsotopes
    fragmented_smi_noIsotopes = Chem.MolToSmiles(modifiedMol,isomericSmiles=True)

    valid = True
    fragments = fragmented_smi_noIsotopes.split(".")

    #check if its a valid triple cut
    if(isotope == 3):
        valid = False
        for f in fragments:
            matchObj = re.search( '\*.*\*.*\*', f)
            if matchObj:
                valid = True
                break

    if valid:
        if(isotope == 1):
            fragmented_smi_noIsotopes = re.sub('\[\*\]', '[*:1]', fragmented_smi_noIsotopes)

            fragments = fragmented_smi_noIsotopes.split(".")

            #print fragmented_smi_noIsotopes
            s1 = Chem.MolFromSmiles(fragments[0])
            s2 = Chem.MolFromSmiles(fragments[1])

            #need to cansmi again as smiles can be different
            output = '%s,%s,,%s.%s' % (smi,id,Chem.MolToSmiles(s1,isomericSmiles=True),Chem.MolToSmiles(s2,isomericSmiles=True) )
            if( (output in out) == False):
                out.add(output)

        elif (isotope >= 2):
            #add the isotope labels
            for key in isotope_track:
                #to add isotope lables
                modifiedMol.GetAtomWithIdx(key).SetIsotope(isotope_track[key])
            fragmented_smi = Chem.MolToSmiles(modifiedMol,isomericSmiles=True)

            #change the isotopes into labels - currently can't add SMARTS or labels to mol
            fragmented_smi = re.sub('\[1\*\]', '[*:1]', fragmented_smi)
            fragmented_smi = re.sub('\[2\*\]', '[*:2]', fragmented_smi)
            fragmented_smi = re.sub('\[3\*\]', '[*:3]', fragmented_smi)

            fragments = fragmented_smi.split(".")

            #identify core/side chains and cansmi them
            core,side_chains = find_correct(fragments)

            #now change the labels on sidechains and core
            #to get the new labels, cansmi the dot-disconnected side chains
            #the first fragment in the side chains has attachment label 1, 2nd: 2, 3rd: 3
            #then change the labels accordingly in the core

            #this is required by the indexing script, as the side-chains are "keys" in the index
            #this ensures the side-chains always have the same numbering

            isotope_track = {}
            side_chain_fragments = side_chains.split(".")

            for s in xrange( len(side_chain_fragments) ):
                matchObj = re.search( '\[\*\:([123])\]', side_chain_fragments[s] )
                if matchObj:
                    #add to isotope_track with key: old_isotope, value:
                    isotope_track[matchObj.group(1)] = str(s+1)

            #change the labels if required
            if(isotope_track['1'] != '1'):
                core = re.sub('\[\*\:1\]', '[*:XX' + isotope_track['1'] + 'XX]' , core)
                side_chains = re.sub('\[\*\:1\]', '[*:XX' + isotope_track['1'] + 'XX]' , side_chains)
            if(isotope_track['2'] != '2'):
                core = re.sub('\[\*\:2\]', '[*:XX' + isotope_track['2'] + 'XX]' , core)
                side_chains = re.sub('\[\*\:2\]', '[*:XX' + isotope_track['2'] + 'XX]' , side_chains)

            if(isotope == 3):
                if(isotope_track['3'] != '3'):
                    core = re.sub('\[\*\:3\]', '[*:XX' + isotope_track['3'] + 'XX]' , core)
                    side_chains = re.sub('\[\*\:3\]', '[*:XX' + isotope_track['3'] + 'XX]' , side_chains)

            #now remove the XX
            core = re.sub('XX', '' , core)
            side_chains = re.sub('XX', '' , side_chains)

            output = '%s,%s,%s,%s' % (smi,id,core,side_chains)
            if( (output in out) == False):
                out.add(output)

def fragment_mol(smi,id):

    mol = Chem.MolFromSmiles(smi)

    #different cuts can give the same fragments
    #to use outlines to remove them
    outlines = set()

    if(mol == None):
        sys.stderr.write("Can't generate mol for: %s\n" % (smi) )
    else:
        #SMARTS for "acyclic and not in a functional group"
        smarts = Chem.MolFromSmarts("[#6+0;!$(*=,#[!#6])]!@!=!#[*]")

        #finds the relevant bonds to break
        #find the atoms maches
        matching_atoms = mol.GetSubstructMatches(smarts)

        total = len(matching_atoms)

        #catch case where there are no bonds to fragment
        if(total == 0):
            output = '%s,%s,,' % (smi,id)
            if( (output in outlines) == False ):
                outlines.add(output)

        bonds_selected = []

        #loop to generate every single, double and triple cut in the molecule
        for x in xrange( total ):
            #print matches[x]
            bonds_selected.append(matching_atoms[x])
            delete_bonds(smi,id,mol,bonds_selected,outlines)
            bonds_selected = []

            for y in xrange(x+1,total):
                #print matching_atoms[x],matching_atoms[y]
                bonds_selected.append(matching_atoms[x])
                bonds_selected.append(matching_atoms[y])
                delete_bonds(smi,id,mol,bonds_selected,outlines)
                bonds_selected = []

                for z in xrange(y+1, total):
                    #print matching_atoms[x],matching_atoms[y],matching_atoms[z]
                    bonds_selected.append(matching_atoms[x])
                    bonds_selected.append(matching_atoms[y])
                    bonds_selected.append(matching_atoms[z])
                    delete_bonds(smi,id,mol,bonds_selected,outlines)
                    bonds_selected = []

            #right, we are done.

    return outlines

if __name__=='__main__':

    if (len(sys.argv) >= 2):
	print "Program that fragments a user input set of smiles.";
	print "The program enumerates every single,double and triple acyclic single bond cuts in a molecule.\n";
	print "USAGE: ./rfrag.py <file_of_smiles";
	print "Format of smiles file: SMILES ID (space separated)";
	print "Output: whole mol smiles,ID,core,context\n";
	sys.exit(1)

    #read the STDIN
    for line in sys.stdin:

        line = line.rstrip()

        line_fields = re.split('\s|,',line)
        smiles = line_fields[0]
        cmpd_id = line_fields[1]

        #returns a set containing the output
        o = fragment_mol(smiles,cmpd_id)

        for l in o:
            print l