#!/usr/local2/bin/python2.3
import os, string
from openeye.oechem import *

rxn = 3
ifs = oemolistream()
ifs.open('ORIGINAL_MOLS/a4_kegg_012506.ism')
ofs_1 = oemolostream()
ofs_2 = oemolostream()
ofs_1.open('b'+str(rxn)+'_ln.ism')
ofs_2.open('b'+str(rxn)+'_lp.ism')

mol_hyd = OEGraphMol()
OEParseSmiles(mol_hyd, "[OH-]")
# Reaction 3: OH-H nucleophilic attack at N-C=X (X(not CvO) endocyclic or chain member) (amidine, guanidine) NON_AROMATIC
# leaving amine not protonated 
libgen1 = OELibraryGen("[H,A:4][C:1]([N:2])=[!C&!O:3].[O-:100][H:99]>>[H,A:4][C:1]([N:2])([O-:100])[*:3][H:99]")

libgen1.SetExplicitHydrogens(True)
libgen1.SetValenceCorrection(False)

for mol in ifs.GetOEMols():
    libgen1.AddStartingMaterial(mol, 0)
    libgen1.AddStartingMaterial(mol_hyd, 1)
    mol.Clear()
    mol_hyd.Clear()

title_list = []

rxn_n = 1
while rxn_n < rxn:
    old_title_file = open('b'+str(rxn_n)+'_ln.ism','r')
    for title in old_title_file.readlines():
        title_list.append(string.split(title)[1])
    old_title_file.close()
    old_title_file = open('b'+str(rxn_n)+'_lp.ism','r')
    for title in old_title_file.readlines():
        title_list.append(string.split(title)[1])
    old_title_file.close()
    rxn_n+=1

for products in libgen1.GetProducts():
    num = 1
    prot = 0
    title = products.GetTitle()+str(num)+'p'+str(prot)
    while title in title_list:
        num+=1
        title = products.GetTitle()+str(num)+'p'+str(prot)
    title_list.append(title)
    products.SetTitle(title)
    OEWriteMolecule(ofs_1, products)

ofs_1.close()
ifs.close()

# Protonation Reaction 3: Protonation of all possible leaving groups (amines) of reaction 3 - not doable in one step,
# because in case of 2 Ns each needs to be protonated one time
# protonation of leaving amine - will generate identical molecules if similar N:2 twice bonded to C:4

ifs.open('b'+str(rxn)+'_ln.ism')

mol_prot = OEGraphMol()
OEParseSmiles(mol_prot, "[H+]")
libgen2 = OELibraryGen("[CX4v4:1]([N:2])[O-:100].[H:99]>>[C:1]([N+:2][H:99])[O-:100]")

for mol in ifs.GetOEMols():
    libgen2.AddStartingMaterial(mol, 0)
    libgen2.AddStartingMaterial(mol_prot, 1)
    mol.Clear()
    mol_prot.Clear()

product_smiles = []

for products in libgen2.GetProducts():
    if OECreateIsoSmiString(products) in product_smiles:
        continue
    else:
        product_smiles.append(OECreateIsoSmiString(products))
    prot = 0
    title = products.GetTitle()[:string.find(products.GetTitle(), 'p0')]+'p'+str(prot)
    while title in title_list:
        prot+=1
        title = products.GetTitle()[:string.find(products.GetTitle(), 'p')]+'p'+str(prot)
    title_list.append(title)
    products.SetTitle(title)
    OEWriteMolecule(ofs_2, products)

ofs_2.close()
ifs.close()