[gmx-users] Hamiltonian Replica Exchange

Szilárd Páll pall.szilard at gmail.com
Wed Jun 25 18:21:21 CEST 2014


Next time, you should perhaps use "plz, ..." (and other eye-catching
formatting marks); a nice mix of font colors and typefaces could also
help to highlight your questions. :D

On Tue, Jun 24, 2014 at 10:32 PM, Thomas Evangelidis <tevang3 at gmail.com> wrote:
> Greetings,
> I want to use the HREX implementation of GROMACS to study the dynamics of a
> heterodimeric protein. The structure is a two helix bundle (two helical
> monomers that are wrapped around each other) with disordered ends. I am
> mainly interested in the dynamics of the disordered ends because I know
> from NMR that the rest remains structured.

> My question is, can I scale
> selectively the Hamiltonian of the disordered ends whilst leaving the
> Hamiltonian of the rest of the protein untouched in order to preserve the
> dimeric structure?

I'm no expert in protein simulations, so take this with a grain of salt. ;)

Unless your helix bundle is rather unstable, I think your proposal is
fine. However, why not try it first? Generate the scaled topologies
and run the one with the highest effective temperature separately to
assess the stability of the bundles.

> Otherwise I 'll have to impose distance and secondary structure restraints
> which will slow down the computations and render the dynamics of the
> structured part unphysical. Is it possible to increase the force constant
> of the harmonic restraints as lambda decreases to attenuate the stiffness
> of the helices?

Restraints are indeed sometimes required (and the above suggested
experiment should tell whether that's the case, I think), but the
lucky thing in the less than ideal topology hacking-based PLUMED
approach is that you will actually by definition have N different
inputs which can have differences not only in the scaled interactions,
but e.g. in restraint strength.

> The other alternative will be to use much fewer replicas (up to lambda ~0.8
> to be on the safe side) thus with slower sampling.

If you want to be on the safe side and you observe is a sudden change
in the stability of the helix bundle from a certain lambda, you can
just stick to scaling factors lower than this. Assessing what maximum
lambda is reasonable is something you should probably anyway do.


> thanks,
> Thomas
> --
> ======================================================================
> Thomas Evangelidis
> PhD student
> University of Athens
> Faculty of Pharmacy
> Department of Pharmaceutical Chemistry
> Panepistimioupoli-Zografou
> 157 71 Athens
> email: tevang at pharm.uoa.gr
>           tevang3 at gmail.com
> website: https://sites.google.com/site/thomasevangelidishomepage/
> --
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