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()
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…
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
Silicos-it provides nice chemoinformatic tools.
