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# Created by Jameed Hussain, July 2013

import sys
import re
from optparse import OptionParser
from rdkit import Chem
from rdkit.Chem import AllChem

def smiles_to_smarts(smi):
    mol = Chem.MolFromSmiles(smi)

    if(mol is None):
        sys.stderr.write("Can't generate mol for: %s\n" % (smi) )
        return None

    #change the isotope to 42
    for atom in mol.GetAtoms():
        atom.SetIsotope(42)

    #preint out the smiles - all the atom attributes will be fully specified
    smarts = Chem.MolToSmiles(mol,isomericSmiles=True)
    #remove the 42 isotope labels
    smarts = re.sub(r'\[42', "[", smarts)
    #now have a fully specified SMARTS - simples!

    return smarts

if __name__=='__main__':

    parser = OptionParser(description="Program to apply transformations to a set of input molecules",
                    epilog="Example command: mol_transform.py -t TRANSFORM_FILE <SMILES_FILE\t\t"
                    "Format of smiles file: SMILES ID <space or comma separated>\t\t\t"
                    "Format of transform file: transform <one per line>\t\t\t"
                    "Output: SMILES,ID,Transfrom,Modified_SMILES")
    parser.add_option('-f','--file',action='store', dest='transform_file', type='string',
                      help='The file containing the transforms to apply to your input SMILES')

    (options, args) = parser.parse_args()

    #print options.transform_file
    if(options.transform_file == None):
        print "Please specify the transform file."
        sys.exit(1)

    smiles=[]
    #read the STDIN
    for line in sys.stdin:
        line = line.rstrip()
        smi,id = re.split('\s|,',line)
        #print smiles,id
        smiles.append( (smi,id) )

    #read the transform file
    #all the transform must come from BioDig to guarantee they have been cansmirk'ed
    infile=open(options.transform_file, 'r')

    print "Input_SMILES,ID,RG-Transform,RG-transformedSMILES"
    for transform in infile:
        transform = transform.rstrip()

        #need to conver the smiles to smart to get rid of any potential issues
        lhs,rhs = transform.split(">>")

        if(lhs == "[*:1][H]"):
            lhs = "[*;!H0:1]"
        else:
            lhs = smiles_to_smarts(lhs)

        if(rhs == "[*:1][H]"):
            rhs = "[*:1]"
        else:
            rhs = smiles_to_smarts(rhs)

        rdkit_transform = "%s>>%s" % (lhs,rhs)
        rxn = AllChem.ReactionFromSmarts(rdkit_transform)
        #rxn = AllChem.ReactionFromSmarts(transform)

        for x in smiles:           
            mol = Chem.MolFromSmiles( x[0] )            
            ps = rxn.RunReactants( [mol] )

            products = set()
            for y in xrange(len(ps)):
                for z in xrange(len(ps[y])):
                    p = ps[y][z]
                    Chem.SanitizeMol(p)
                    products.add(Chem.MolToSmiles(p,isomericSmiles=True))

            for p in products:
                print "%s,%s,%s,%s" % (x[0],x[1],transform,p)