[gmx-developers] Problems with artificial minima when using soft-core potentials

Shirts, Michael (mrs5pt) mrs5pt at eservices.virginia.edu
Mon Sep 3 21:22:58 CEST 2012

BTW, I'm very happy to add this to 5.0 moving forward as an alternate
approach -- although the CHOICE of separate parameters is complicated, the
coding is not. The cases are already handled separately 4.6 to support the
separation of coul and vdw so making them separate variables is easy.  I
just don't think we can add it to 4.6 at this point in the development

I'll also note that we are working in my group in a way of avoiding softcore
calculations entirely -- but that's not quite ready to be unveiled yet.

Michael Shirts
Assistant Professor
Department of Chemical Engineering
University of Virginia
michael.shirts at virginia.edu

> From: Bert de Groot <bgroot at gwdg.de>
> Reply-To: Discussion list for GROMACS development <gmx-developers at gromacs.org>
> Date: Mon, 3 Sep 2012 19:08:12 +0200
> To: Discussion list for GROMACS development <gmx-developers at gromacs.org>
> Subject: Re: [gmx-developers] Problems with artificial minima when using
> soft-core potentials
> Dear Alan,
> thank you for bringing this up.
> Just to put a few things straight:
> -the first thing we tried when running into softcore instabilities was to
> adopt 
> the Beutler approach with separate alpha values for the LJ and Coulombic
> interactions. This indeed helps to a certain extent (as does Berk's fix for
> hydrogens). However, both approaches still lead to additional minima at
> intermediate lambda values for certain atom types, which cannot be avoided by
> any choice of separate alpha values for LJ and Coulomb interactions (or at
> least 
> not for any combination we tried). We explore this in Fig S4 of our paper. The
> artificial minima particularly occur when using fast-growth methods and
> frequently involved . Unfortunately the effect can easily remain unnoticed and
> therefore lead to inaccurate free energy estimates. This issue is solved in
> our 
> softcore approach.
> It may be that the systematic approach by Steinbrecher and Case mentioned by
> Michael Shirts yields suitable alpha values for the original Beutler softcore
> also in the cases that we found to be problematic. This would be interesting
> to 
> test.
> -you mention that the potential has a discontinuity at r=0 in our approach,
> which may lead to potentially unstable dynamics. This is not the case. Only
> the 
> force is discontinuous (just like the hardcore LJ and Coulomb forces are
> discontinuous at r=0). This does not lead to unstable dynamics. In addition,
> also the discontinuous force is not an issue, simply because r=0 is never
> reached. This holds in the hardcore case as well as in our case. Now one could
> argue that with a softcore potential r=0 might be more easily reached than in
> the hardcore case, because of a lower enthalpic cost. This is indeed true, but
> as we explore in section S4 of our paper, even in single precision the
> probability to hit r=0 is negligible for all practical purposes, not only for
> enthalpic but particularly for entropic reasons.
> Our softcore implementation is currently obtainable as patch for gromacs
> 4.0.7, 
> and will soon (when we're done testing) be available for 4.5 and commited to
> git 
> for future gromacs releases (4.6 or master).
> best regards,
> Bert
> ______________________________________
> Prof. Bert de Groot, Ph.D.
> Max Planck Institute for Biophysical Chemistry
> Computational biomolecular dynamics group
> Am Fassberg 11
> 37077 Goettingen, Germany
> tel: +49-551-2012308, fax: +49-551-2012302
> http://www.mpibpc.mpg.de/groups/de_groot
> On 09/03/2012 05:08 PM, Alan E. Mark wrote:
>> Dear Berk,
>>              This has been coming up in various circumstances for a long
>> time.
>> Bert de Groot recently however published a paper in JCTC highlighting the
>> problem in GROMACS and proposing a complex solution which in fact makes the
>> potential have a discontinuity at r=0. This also makes the dynamics
>> potentially
>> unstable. Stable dynamics was exactly why the soft-core was introduced in
>> this
>> form in the first place.  He claims there is a problem with our soft-core
>> when
>> in reality the problem is in the form implemented in GROMACS which is a pity.
>> I
>> would also note that  by being able to scale the alpha parameters for the LJ
>> and
>> electrostatics separately (i.e. using a larger shifting distance for the
>> electrostatics) avoids any need to turn off the electrostatics first. Turning
>> the electrostatics off completely first can add the the range of non-physical
>> states that need to be sampled making the calculations slower and more
>> complex
>> than necessary.
>> Alpesh and I are writing a response to Bert's paper and a few other factors.
>> I
>> will send you a copy when we have a good draft.
>> Alan
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