[gmx-users] General query regarding MD simulation.

Justin Lemkul 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 
inherently deficient.

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.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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