On Wed, 2008-09-03 at 10:08 +0530, Bharat Somkuwar wrote:
> Hi all can anyone suggest me the solution?
> For a small molecule, is their any way (computational) to find out
> formal / overall charge of the molecule at a particular pH?
Ah, I missed the point of your question: You want reliable pKA
computations for small compounds not proteins. Our group has done some
work on that in the past:
It involves calculating the proton affinity in vacuum using DFT,
generating partial charges using RESP and finally it performs two
poisson-boltzmann calculations to get the solvation energy difference
between protonated and deprotonated species. In the assay described in
the paper the author achieved an accuracy of +/- 0.5 pKA unit using
jaguar 4 and B3LYP functional. For small molecules such a calculation is
done within a couple of minutes usually (if you are familiar with Jaguar
To get the ionic state of the molecule bound on the protein you would
have to perform a PB pKA calculation using the charges you generated in
the ab-initio step and adding the energy shift caused by the protein
environment to the pKA value of the molecule in aqueous solution.