On 2/15/13 4:00 PM, Abhishek Acharya wrote:
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).
I think i would try both approaches.
In regard to the derivation of ff compatible parameters, i see that for
ff's like AMBER94 one resorts to ab-initio 6-31G* calculations and fitting
to electrostatic potential surfaces. But for OPLSaa, if one goes through
the literature, it says, 'the charges for OPLS are empirical and have
been obtained largely from fitting to reproducible properties of organic
liquids.The charges for functional groups are taken to be transferable
between molecules and the use of neutral subunits makes the derivation of
charges for large molecules straightforward.'
I presume the first line means charges were derived from experimental
data. But I didn't understand what the last line means. Kindly help!!
Empirical charge derivation, in a sense, means the authors fiddled with it until
it worked ;) In seriousness though, generally some preliminary QM calculations
are done to obtain charge distribution, and then adjustments made to fit with
known experimental data. For OPLS, it's typically properties of liquids that
serve as model compounds for the desired molecule. The derivation is thus done
in terms of functional groups, not necessarily whole molecules. That's where
the last line comes in - you can piece molecules together based on universal
(supposedly), transferable groups whose parameters do not depend on the rest of
the molecule. For instance, GDP would not be derived directly, but its
components would, and then the molecule would be pieced together from various
functional groups (imidazole, amines, carbonyl compounds, etc).
-Justin
--
========================================
Justin A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
========================================
--
gmx-users mailing list [email protected]
http://lists.gromacs.org/mailman/listinfo/gmx-users
* Please search the archive at
http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
* Please don't post (un)subscribe requests to the list. Use the
www interface or send it to [email protected].
* Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
