Re: Protein RMSF in replica exchange simulations

From: Brian Radak (
Date: Mon Jan 25 2021 - 16:22:39 CST

Hi Victor,

How you calculate any observable (including RMSF) with replica exchange
depends on the implementation. I'm pretty sure (although I might be
wrong) that all of the REMD scripts distributed with NAMD track replicas
(i.e. the state parameter, here the REST2 "temperature", changes over
the course of the trajectory).

In this case, the RMSF should be the same over all trajectories within
statistical uncertainty. This also means that:

  1. The trajectory statistics can be pooled under the assumption that
they are independent

  2. Any differences across trajectories are entirely sampling artifacts.

I would also contend that the RMSF computed this way is a completely
unphysical quantity that only gives you an impression of sampling
efficiency. It does not even describe real population thermodynamics.
For that you would have to apply a WHAM-like scheme. I don't know if any
scripts for that purpose are readily available.



On 1/25/21 4:50 PM, Victor Zhao wrote:
> Dear all,
> I have been running replica exchange simulations (REST2). So far, I
> have focused on observables calculated on a per-frame basis and
> averaged to obtain ensemble values. But I am wondering, is it useful
> to calculate RMSF in a replica exchange simulation? Presumably you
> would do it over the replica index of interest (i.e. replica 0). But
> the trajectory at each replica setting includes exchanges between
> replicas. And yet I’ve read papers where RMSF is still calculated in
> replica exchange simulations.
> Often, RMSF calculations presented in papers don’t appear to make a
> larger point beyond that different parts of the protein differ in
> flexibility, so I think RMSF calculations in a replica exchange
> simulation could serve the same purpose. But when it comes to the
> issue of comparing RMSF between different replica exchange
> simulations, wouldn’t different exchange acceptance rates prevent
> comparison between simulations? That is, suppose one simulation has a
> 0 <-> 1 exchange rate of 0.2 whereas another has an exchange rate of
> 0.25. In this case, the average time between exchanges would be
> different, which could affect RMSF. I am wondering what the experts on
> this list think.
> Best regards,
> Victor Zhao
> PhD Candidate, Chemistry
> Shakhnovich Lab, Harvard University
> <>

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