I would like some help on using the Pharmacophore matching code in RDKit.
I am trying to screen molecules using 3D pharmacophores, and I am not totally
sure I'm going about it correctly. I start with a known
3D structure of a ligand, and want to use EmbedMol() to try and find molecules
that can be made fit the molecule derived from this.
To build a pharmacophore from chemical features in a 3D molecule, I have been
doing something like:
from rdkit import Chem
from rdkit import Geometry
from rdkit import RDConfig
from rdkit.Chem import AllChem
from rdkit.Chem.Pharm3D import Pharmacophore, EmbedLib
m1 = Chem.MolFromMolFile('example.sdf')
FEATURE_DEF_FILE = os.path.join(RDConfig.RDDataDir,'BaseFeatures.fdef')
feat_factory = ChemicalFeatures.BuildFeatureFactory(FEATURE_DEF_FILE)
feats = feat_factory.GetFeaturesForMol(m1)
pcophore = Pharmacophore.Pharmacophore(feats)
I'm reasonably confident that this is correct. Where I am having trouble is
with what exactly the bounds matrix is supposed to represent,
and how to supply the atomMatch parameter to EmbedMol.
I am assuming something like:
bounds_matrix = AllChem.GetMoleculeBoundsMatrix(m1)
m2 = Chem.MolFromSmiles('c1ccccc1C(=O)N')
can_match, atomMatch = EmbedLib.MatchPharmacophoreToMol(m2, feat_factory,
pcophore)
if can_match:
EmbedLib.EmbedPharmacophore(m2, atomMatch, pcophore,
bounds=bounds_matrix)
Which should add a conformer to m2. Is this the best way to do it?
Also, what is the correct way to use excluded volumes. I originally assumed
that they were implemented as a sphere with
an x,y,z coordinate centre, and a certain radius, but that does not seem to be
the case from looking at the documentation.
Thanks,
Fergal Duffy
------------------------------------------------------------------------------
Introducing AppDynamics Lite, a free troubleshooting tool for Java/.NET
Get 100% visibility into your production application - at no cost.
Code-level diagnostics for performance bottlenecks with <2% overhead
Download for free and get started troubleshooting in minutes.
http://p.sf.net/sfu/appdyn_d2d_ap1
_______________________________________________
Rdkit-discuss mailing list
[email protected]
https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
