Re: Simulation of a protein and calcium ions

From: Kenno Vanommeslaeghe (
Date: Tue Oct 08 2013 - 11:37:19 CDT

I see 3 potential sources of trouble that need to be taken into account:

- The simulation time scale, as pointed out by Axel. I would say a 5ns
protein simulation is too short for most purposes; something like 50ns
would be better.
- The force field, as pointed out by Ajasja. In additive force fields, our
experience is indeed that without NBFIX, it is impossible to find LJ
parameters that both reproduce the RDF in water and the specific binding
to protein side chains. It is not impossible that calcium will bind too
weakly in the CHARMM force field (though it could be too strongly too). At
any rate, getting no binding at all would be a bit surprising.
- The ionization state of the side chains! The presence of a Ca2+ will
make all basic side chains less basic and acidic side chains more acidic.
In nature, weakly acidic side chains can dynamically deprotonate to allow
a Ca2+ ion to bind, but in a Class I force field, this is obviously
impossible (except when doing constant pH simulations). To see the
experimentally observed binding, you may need to try a few ionization
states, including ones that would seem slightly unfavorable at neutral pH.

On 10/08/2013 04:15 AM, Stephan Matthias Grein wrote:
> Hash: SHA1
> Dear NAMD users,
> after a couple of weeks learning the NAMD/VMD basics, i came up with
> one question i could not figure myself:
> I have generated PSF/PDB files for my protein of interest, using
> consistent topoplogy and force field parameter files and a consistent
> NAMD script setup. Solvated this in a waterbox with PBC according to
> the manual - which works fine.
> I'm now interested in observing ions moving into binding pockets of
> the protein (which are reported by literature to be between some EC
> domains of the protein)... for that i solvated my protein with various
> concentrations using the AutoSolvation tool in VMD.
> However, at neither a low nor an extraordinary (unphysiologically)
> high ion concentration, i could observe ions moving into the binding
> pockets of the protein and which should stay there, according to
> literature, at least if the ion concentration is very high.
> Is there a general failure with my procedure? If yes, would you mind
> to point it out?
> Thanks in advance,
> Stephan
> - --
> M. Sc. Stephan Grein
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