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.