Re: Simulation of a protein and calcium ions

From: Stephan Matthias Grein (grein_at_informatik.uni-frankfurt.de)
Date: Wed Oct 09 2013 - 02:39:27 CDT

Thank you very much.

I will investigate these things.
One problem remains: AutoPSF Buider removes the crystallographically
resolved Calcium ions from my .psf and .pdb files, why? And how can I
avoid this?

All the best,
Stephan
Am 10/8/13 6:37 PM, schrieb Kenno Vanommeslaeghe:
> 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:
> 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
>
>>

This archive was generated by hypermail 2.1.6 : Tue Dec 31 2013 - 23:23:49 CST