Hello All,
I am trying to re-shuffle the side-chain(s) identified after replacing core
(MCS between two mols) from molecules. The two molecules I am considering
are BMS-193884 and irbesartan. Both molecules share biphenyl framework and
act on different target (antagonist of ETA and AT1 respectively). The
approach I have taken is to replace side-chain(s) of BMS-193884 with the
side-chain(s) of irbesartan and vice-versa using ReplaceSubstructs to
generate new molecules keeping MCS as a core part.
I have pasted minimal code below this mail. I do not know whether this
would be correct approach or not?
Moreover, I am getting dummy atoms in some of the output molecules.
Any help/guidance would be greatly appreciated.
Thanks
Om Prakash
Ph.D Student
School of Computational and Integrative Sciences,
Jawaharlal Nehru University,
New Delhi,
India
#================================
from rdkit.Chem import MCS
from rdkit import Chem
from rdkit.Chem import AllChem
import re
mol1 =
Chem.MolFromSmiles("CCCCC1=NC2(CCCC2)C(=O)N1C1=CC=C(C=C1)C1=C(C=CC=C1)C1=NNN=N1")
mol1.SetProp("_Name","Irbesartan")
mol2 =
Chem.MolFromSmiles("CC1=NOC(NS(=O)(=O)C2=CC=CC=C2C2=CC=C(C=C2)C2=NC=CO2)=C1C")
mol2.SetProp("_Name","BMS-193884")
mols = [mol1,mol2]
# Get mcs
out=MCS.FindMCS(mols,completeRingsOnly=True)
core = Chem.MolFromSmarts(out.smarts)
# Get chain and chain fragments for mol1
chains = Chem.ReplaceCore(mol1,core)
# replace dummy atoms and make RDMol
subchainsMol1=[Chem.MolFromSmiles(re.sub("\[?\d\*\]","",Chem.MolToSmiles(x,True)))
for x in Chem.GetMolFrags(chains,asMols=True)]
#[Chem.MolToSmiles(x,True) for x in Chem.GetMolFrags(chains,asMols=True)]
#['[*]N1C(=O)C2(CCCC2)N=C1CCCC', '[*]c1nn[nH]n1']
# Get chains and chain fragments for mol2
chains = Chem.ReplaceCore(mol2,core)
# replace dummy atoms and make RDMol
subchainsMol2=[Chem.MolFromSmiles(re.sub("\[?\d\*\]","",Chem.MolToSmiles(x,True)))
for x in Chem.GetMolFrags(chains,asMols=True)]
#[Chem.MolToSmiles(x,True) for x in Chem.GetMolFrags(chains,asMols=True)]
#['[*]S(=O)(=O)Nc1onc(C)c1C', '[*]c1ncco1']
# Build dictionary of various mols
allReplacements={}
for i,x in enumerate(subchainsMol1):
for j,y in enumerate(subchainsMol2):
allReplacements[i,j,mol1]=AllChem.ReplaceSubstructs(mol1,x,y)
for i,x in enumerate(subchainsMol2):
for j,y in enumerate(subchainsMol1):
allReplacements[i,j,mol2]=AllChem.ReplaceSubstructs(mol2,x,y)
for keys,values in allReplacements.items():
print Chem.MolToSmiles(values[0],True)
Output:
CCCCC1=NC2(CCCC2)C(=O)N1c1ccc(-c2ccccc2-c2nn[nH]n2)cc1
Cc1noc(NS(=O)(=O)c2ccccc2-c2ccc(-c3nn[nH]n3)cc2)c1C
CCCCC1=NC2(CCCC2)C(=O)N1c1ccc(-c2ccccc2-c2nn[nH]n2)cc1
CCCCC1=NC2(CCCC2)C(=O)N1[*]c1ccc(-c2ccccc2S(=O)(=O)Nc2onc(C)c2C)cc1
CCCCC1=NC2(CCCC2)C(=O)N1c1ccc(-c2ccccc2-c2ncco2)cc1
CCCCC1=NC2(CCCC2)C(=O)N1[*]c1ccccc1-c1ccc(-c2ncco2)cc1
CCCCC1=NC2(CCCC2)C(=O)N1c1ccc(-c2ccccc2S(=O)(=O)Nc2onc(C)c2C)cc1
c1coc(-c2ccc(-c3ccccc3-c3nn[nH]n3)cc2)n1
------------------------------------------------------------------------------
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