Try to subshape alignment

Molecular shape based alignment is useful for VS, scaffold hopping, etc.
ROCS is very popular tool to do it.
But there are some another tools.
I found nice reference on web, and tried to do subshape alignment using RDKit.
My try was failed because it took very long time ;-(.
This is snippet..
” I down load sdf from PubChem, all mols were similar to imatinib. ”

from rdkit import Chem
from rdkit.Chem import AllChem
from rdkit import RDConfig
from rdkit.Chem.Draw import IPythonConsole
from rdkit.Chem import Draw
from rdkit.Chem import PyMol
import os
mols = [ Chem.AddHs(m) for m in Chem.SDMolSupplier("sample.sdf")]

Them make viewer object. (Pymol must be run at server-mode.)
And generate conformers for each molecules.

v = PyMol.MolViewer()
for mol in mols:
    cids = AllChem.EmbedMultipleConfs(mol, pruneRmsThresh=1.0)

for idx in range(len(mols)):
    mol = mols[idx]
    for cid in cidslist[idx]:
        AllChem.UFFOptimizeMolecule(mol, confId=cid)

Now, I could get 3d grid image.

Draw.MolsToGridImage(mols[:5], molsPerRow=5)


Next, import Subshape module.

from rdkit.Chem.Subshape import SubshapeBuilder, SubshapeAligner, SubshapeObjects

Then, make ref and probe molecule and each mol’s shapes following command.

ref = Chem.Mol(mols[0].ToBinary())
probe = Chem.Mol(mols[1].ToBinary())
builder = SubshapeBuilder.SubshapeBuilder()
builder.gridDims = (20.,20.,10.)
builder.winRad = 4.

refShape = builder.GenerateSubshapeShape(ref)
probeShape = builder.GenerateSubshapeShape(probe)

Draw ref mol and ref_shape.

SubshapeObjects.DisplaySubshape(v,refShape,'ref_Shape')'set transparency=0.5')

It looks like good.

Align two molecules.

aligner = SubshapeAligner.SubshapeAligner()
algs = aligner.GetSubshapeAlignments(ref,refShape,probe,probeShape,builder)

In this step, my mac book air looks like freeze…. So, I canceled this step.
It was hard to me to do it using RDKit. Hmm…

If you want to know more details, please read following link.


Published by iwatobipen

I'm medicinal chemist in mid size of pharmaceutical company. I love chemoinfo, cording, organic synthesis, my family.

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