Dear All,
Apologies for posting on a rather well-trodden (and tedious?) topic...
I have just spent some time counting H-bond donors in a variety of ways
for a 4000 compound data set - to see how our calculations could best
match the results coming from a collaborator (it's as fun as it sounds).
As it turns-out, Descriptors.NumHDonors is pretty much on the money! (ie
counting the number or N and O atoms that have at least one H attached)
However, during this process I ended-up going back to a (the?) Lipinski
paper -
Christopher A Lipinski, Franco Lombardo, Beryl W Dominy, Paul J Feeney,
Experimental and computational approaches to estimate solubility and
permeability in drug discovery and development settings, Advanced Drug
Delivery Reviews, Volume 46, Issues 1-3, 1 March 2001, Pages 3-26, ISSN
0169-409X, 10.1016/S0169-409X(00)00129-0.
- to see what the Lipinski definition of Hydrogen Bond Donors was. I
read the following:
"We found that simply adding the number of NH bonds and OH bonds does
remarkably well as an index of H bond donor character. Importantly, this
parameter has direct structural relevance to the chemist."
As far as I can tell, this would require explicit addition of Hs to the
molecule, followed by counting the number of matches for an NH or OH
BOND; something like the following:
>>> from rdkit import Chem
>>> from rdkit.Chem import Descriptors
>>> smarts = Chem.MolFromSmarts("[#7,#8]-[#1]")
>>> mol = Chem.MolFromSmiles("CC(=O)N")
>>> mol = Chem.AddHs(mol)
>>> matches = mol.GetSubstructMatches(smarts)
>>> print len(matches)
2
The MOE descriptor lip_don seems to exactly reproduce these 'bond count'
numbers for my set of compounds. So I guess my question is - shouldn't
we be counting the NH and OH bonds for Lipinski-like counting? (and I
guess this is what MOE's lip_don is for)
Kind regards
James
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Dr James Davidson
Senior Team Leader,
Medicinal & Computational Chemistry
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