[gmx-users] General query regarding MD simulation.
jalemkul at vt.edu
Fri Feb 15 20:49:21 CET 2013
On 2/15/13 1:29 PM, Abhishek Acharya wrote:
> Dear GROMACS Users.
> Just out of curiosity, i would like to pose a general question here ( i
> didn't have an idea of any other suitable forum ). My protein active site
> has a GDP which is coordinated to a Mg ion. The Mg ion itself coordinates
> two water molecules and is held in position via non-bonded interactions
> from two active site residues. For such a system, I could do two things:
> 1. Do the charge calculation for GDP only and assume the charges of other
> active site constituents to be taken from the FF parameter library.
> 2. As suggested by a a person I know, I can do the charge calculation of
> the whole system including the Mg ion, water molecules and the residues.
> The explanation was that since GDP is in coordination to Mg ion, the
> effective charges would be different than on a GDP alone.
> Can anyone explain which one of the above is a correct approach and why ?
> I somehow was not convinced by my co-workers explanation simply
> considering the fact that for each of the amino acids in a protein the
> charges and parameters are taken from the FF library. Going by the given
> explanation, one should then resort to a charge calculation for the whole
> protein system.
In the context of normal MM force fields with fixed charges, option (1) is what
would generally be used. In determining what is more representative of an
actual biological setting, option (2) is more rigorously correct. Force fields
are usually parameterized in a portable way, such that every residue has uniform
parameters independent of its local environment. Thus polarization effects are
treated in an average way, which may not be optimal. Metal ions have especially
polarizing effects on partial charges of nearby residues. Even QM/MM studies
that are 15 years old concluded that fixed charges for such systems are
I guess the bottom line is you have to derive suitable parameters in a way that
is compatible with the original force field. If that means dealing with the
ligand in isolation, so be it. The comparison between the parameters produced
by options (1) and (2) would be very interesting, though, and may ultimately be
necessary in justifying why your proposed model worked (or didn't).
Justin A. Lemkul, Ph.D.
Department of Biochemistry
jalemkul[at]vt.edu | (540) 231-9080
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