On Fri, 3 Jun 2016 18:39:31 -0400
"Hu, Yuan" <yuan.hu.merck.com> wrote:
> I'm interested in calculation the relative binding free energy of
> mutating a ligand dimer AA into dimer BB, where the ligand in the
> dimer has non-covalent interaction with each other, and both fit into
> the same protein pocket. Considering a single atom mutation from
> A->B, is it possible to use TI to calculate the relative binding free
> energy of AA-->BB transformation? What will be the right way to do
> it? Any thoughts or literature references will be appreciated. Thanks.
I don't think there is a "right" way. Technically, you can go
straight from AA to BB in one "step". One question though is how
disruptive this double mutation would be and whether it wouldn't be
better to do AA->AB (or AA->BA).
I would probably look into several variants to see if the overall
thermodynamic cycle is in agreement with the sum of a smaller subset of
cycles. E.g. will AA->AB->BB and AA->BA->BB give the same result as
AA->BB. The subset steps may also give additional insight.
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Received on Sat Jun 04 2016 - 03:30:02 PDT
