Re: [AMBER] Single long pH-REMD simulation vs. several short pH-REMD simulations

From: Eric Lang <eric.lang.bristol.ac.uk>
Date: Mon, 13 Nov 2017 16:07:46 +0000

Hi Bill,


Thank you for your reply.

I understand your suggestion, however it is quite a computationally demanding process to do for REMD simulations.

I guess my question is more: instead of having to wait 500 ns for a pH-REMD simulation to converge, what if I run 2 simulations of 250 ns (that won't converge) in parallel and combine the results? Should I get the same answer as for the single 500 ns run?


Many thanks,


Eric

--
Eric Lang
BrisSynBio Postdoctoral Research Associate Modelling
Centre for Computational Chemistry
School of Chemistry - University of Bristol
Bristol BS8 1TS - United Kingdom
________________________________
From: Bill Ross <ross.cgl.ucsf.edu>
Sent: 13 November 2017 12:04
To: amber.ambermd.org
Subject: Re: [AMBER] Single long pH-REMD simulation vs. several short pH-REMD simulations
What if you split the difference and do a long run, with multiple
shorter ones optionally started by reequilibrating coordinates from
samples along the way? You can watch the progress of the long run, then
as hardware and intuition dictate, spin off new runs along the way or
after the fact.
Bill
On 11/13/17 3:46 AM, Eric Lang wrote:
> Dear CpHMD experts,
>
>
> I have a question regarding explicit water pH-REMD simulations with a large number (for example between 40 and 100) of titrable residues.
>
> It might sounds like a trivial question to you but I cannot seem to make up my mind about it...
>
>
> Based on your experience or tests you have run it is better to run a single long pH-REMD simulation or several shorter ones or are both approaches equivalent?
>
>
> I guess ideally you want to run several long pH-REMD simulations, each having converged, so you can sample well both the protonation space *and* the conformational space, but because of the computational costs associated with pH-REMD, especially for a titration done over several pH units, it is usually not possible to do so. In such kind of situation is it better to run for example 1 x 500 ns of pH-REMD, 2 x 250 ns, 4 x 125 ns of pH-REMD?
>
>
> The answer would be obvious in the case of classical MD, but in the case of pH-REMD you want to reach convergence for the titration of ionisable residues which might take long for 'problematic residues' i.e residues that have a poor fit to the Hill equation and/or that interact strongly with one another and thus have interdependent protonation states. So if you run 2 short pH-REMD simulations, you might not reach convergence for both of those simulations, but if you combine them are you obtaining similar pKa estimates than you would for a twice as long single pH-REMD simulation (that has a much better convergence than two separate runs) ?
>
>
> Multiple pH-REMD simulations will improve the sampling of your conformational space but perhaps it ultimately worsen your pKa estimates because of convergence issues and at the end of the day, it might be better with limited resources to run a single long pH-REMD simulation.
>
>
> Any insights on the matter would be much appreciated.
>
>
> Many thanks,
>
>
> Eric
>
>
>
> --
>
> Eric Lang
>
> BrisSynBio Postdoctoral Research Associate Modelling
> Centre for Computational Chemistry
> School of Chemistry - University of Bristol
> Bristol BS8 1TS - United Kingdom
>
>
>
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Received on Mon Nov 13 2017 - 08:30:03 PST