Pharmacophore based molecular alignment

Sometime pharmacophore based alignment is used for scaffold hopping, virtual screening or etc.
There are lots of famous tools to do that.
Align-it is one of nice tool for mol align I think. It is open source tool.
You can get the tool from silicos-it web site.
http://silicos-it.be.s3-website-eu-west-1.amazonaws.com/index.html
If reader who use OSx, align-it can install by homebrew. 😉

I tested following sample script.
At first, generate 3D structures from smiles strings.

gen3d_from_smi.py

#! /usr/bin/python
# 
import sys
from rdkit import Chem
from rdkit.Chem import AllChem

supplier = Chem.SmilesMolSupplier( sys.argv[1], delimiter='\t', smilesColumn=0,nameColumn=1, titleLine=True )
sdfWriter = Chem.SDWriter( sys.argv[1][:-4] + "_MMFF_gen3D.sdf")

print("NAME\t\tMMFF ENERGY")
print supplier.next()

for i in range( len(supplier) ):
    mol = supplier[i]
    if (mol.HasProp("_Name")):
        molName = mol.GetProp("_Name")
    molH = AllChem.AddHs( mol )
    cids = AllChem.EmbedMultipleConfs(molH, numConfs=1)
    mp = AllChem.MMFFGetMoleculeProperties(molH)
    for cid in cids:
        field = AllChem.MMFFGetMoleculeForceField( molH, mp, confId = cid )
        field.Minimize()
        e = field.CalcEnergy()
        print('{0:}\t\t{1:.3f}\t\t{2:}'.format(molName, e, cid))
        sdfWriter.write(molH, confId = cid)
sdfWriter.close()

3d_before

input command from terminal.

iwatobipen$ python gen3d_from_smi.py cdk2.smi
iwatobipen$ time align-it -r cdk2_ref3d.sdf -d cdk2_MMFF_gen3D.sdf -o align.sdf -p pharmacopore.phar -s score.txt --cutOff 0.3

I uploaded cdk2.smi to githubrepo.
https://github.com/iwatobipen/mmff_test
Chek align.sdf from pymol…

3d_after

Good!
Molecules seems to be aligned with scaffold.
And align-it can report scores like this …
The format is same as shape-it.

ZINC03814457	202.066	ZINC03814457	202.066	202.066	0	202.066	10	1	1	1
ZINC03814457	202.066	ZINC03814459	175.174	132.513	0	132.513	7	0.5415	0.6558	0.7565
ZINC03814457	202.066	ZINC03814460	164.031	132.49	0	132.49	7	0.5671	0.6557	0.8077
ZINC03814457	202.066	ZINC00023543	159.424	132.488	0	132.488	7	0.5785	0.6557	0.831
ZINC03814457	202.066	ZINC03814458	159.424	132.52	0	132.52	7	0.5788	0.6558	0.8312

Finally, align-it has pymol plug-in !
It’s easy to use.
like following

Screen Shot 2015-05-05 at 5.55.10 PM
Screen Shot 2015-05-05 at 5.55.23 PM

Silicos-it provides nice chemoinformatic tools.

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