Re: More FEP using separated topologies

From: David Huggins (djh210_at_cam.ac.uk)
Date: Fri Apr 28 2017 - 03:28:55 CDT

Thanks very much,

This sounds pretty horrific, but I havent tested it yet to see if it works.

If anyone else tries this, I should note that another fix is to switch
off PME, if you can take the hit in terms of run time.

Best wishes,

Dave

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Dr David J. Huggins
University of Cambridge
Department of Chemistry
Lensfield Rd
Cambridge
CB2 1EW
United Kingdom

Phone: +44 (0)1223 763854
Email: djh210_at_cam.ac.uk
Web: http://huggins-lab.tcm.phy.cam.ac.uk/

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

On 26 April 2017 at 15:59, Radak, Brian K <bradak_at_anl.gov> wrote:
> I was actually about to respond with that same suggestion, but reconsidered
> because it is in fact just a horrible kludge. However, that is probably the
> only way at present to accomplish what you want using NAMD internals.
>
> The language for alchDecouple is kind of horrible - the default (off) is to
> remove internal non-bonded interactions within each group. This only changes
> the endpoint at which the group is to be completely uncoupled.
>
> Another option is to modify your PSF via ParmEd
> (https://github.com/ParmEd/ParmEd), which generally handles such topologies
> quite well, even though it was originally designed for AMBER topologies.
>
> HTH,
> Brian
>
> Brian Radak
> Postdoctoral Appointee
> Leadership Computing Facility
> Argonne National Laboratory
>
> 9700 South Cass Avenue, Bldg. 240
> Argonne, IL 60439-4854
> (630) 252-8643
> brian.radak_at_anl.gov
> ________________________________
> From: owner-namd-l_at_ks.uiuc.edu [owner-namd-l_at_ks.uiuc.edu] on behalf of
> Jérôme Hénin [jerome.henin_at_ibpc.fr]
> Sent: Wednesday, April 26, 2017 5:27 AM
> To: David Huggins
> Cc: Namd Mailing List
> Subject: Re: namd-l: More FEP using separated topologies
>
> Hi David,
>
> sorry, I missed your previous reply.
>
> Looking back, my advice doesn't seem that good anymore. I meant for you to
> just use FEP, but I see now that it will not yield the situation you are
> aiming for, since at either end-point of the transformation, one of the
> ligands will be decoupled.
>
> The only way I can think of, which is more of an ugly hack, is to abuse FEP
> at lambda = 0.5, where each ligand is half-coupled. For that you'd need to
> disable soft-core LJ potentials and set the perturbation schedule to plain
> linear:
>
> alchVdwShiftCoeff 0.
> alchElecLambdaStart 0.
> alchVdwLambdaEnd 1.
>
> and then tweak the nonbonded parameters so that the ligand interactions are
> twice as large (ie. double the epsilons and partial charges). Finally you'd
> need to ensure intra-ligand nonbonded interactions are perturbed as well, by
> keeping alchDecouple to its default value, off.
>
> I hope I'm not forgetting something here.
>
> Best,
> Jerome
>
> On 25 April 2017 at 21:10, David Huggins <djh210_at_cam.ac.uk> wrote:
>>
>> Thanks Jerome,
>>
>> Please can you clarify what you mean? Do you suggest increasing the
>> cutoff or using a later version of NAMD?
>>
>> Best wishes,
>>
>> Dave
>>
>>
>> ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
>>
>> Dr David J. Huggins
>> University of Cambridge
>> Department of Chemistry
>> Lensfield Rd
>> Cambridge
>> CB2 1EW
>> United Kingdom
>>
>> Phone: +44 (0)1223 763854
>> Email: djh210_at_cam.ac.uk
>> Web: http://huggins-lab.tcm.phy.cam.ac.uk/
>>
>> ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
>>
>>
>> On 28 May 2016 at 05:00, Jérôme Hénin <jerome.henin_at_ibpc.fr> wrote:
>> > Dear Dave,
>> >
>> > I was reminded today that explicitly excluded atoms are expected to lie
>> > within the cutoff distance. Those exclusions are not required (anymore)
>> > in
>> > standard FEP runs because those atoms belong to separate partitions.
>> > That
>> > might be the way to go for your needs.
>> >
>> > Best,
>> > Jerome
>> >
>> > On 27 May 2016 at 22:21, David Huggins <djh210_at_cam.ac.uk> wrote:
>> >>
>> >> Dear All,
>> >>
>> >> I am trying to implement a NAMD version of the separated topologies
>> >> method from "Separated topologies—A method for relative binding free
>> >> energy calculations using orientational restraints".
>> >>
>> >> I have used alchemify to switch off interactions between two ligands
>> >> in a protein binding site and the protocol requires me to run dynamics
>> >> where both ligands are fully coupled to the system (though not to each
>> >> other).
>> >>
>> >> However, the resulting simulations always exit early with a "Low
>> >> global exclusion count". I have tried gentle heating and reduced
>> >> timesteps but neither works.
>> >>
>> >> Does anyone have any experience of running simulations where two fully
>> >> coupled species are overlapping and have no mutual interactions?
>> >>
>> >> Best wishes,
>> >>
>> >> Dave
>> >>
>> >>
>> >> ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
>> >>
>> >> Dr David J. Huggins
>> >> MRC New Investigator
>> >> Theory of Condensed Matter Group
>> >> Cavendish Laboratory
>> >> JJ Thomson Avenue
>> >> Cambridge, CB3 0HE
>> >> United Kingdom
>> >>
>> >> Phone: +44 (0)1223 764164
>> >> Fax: +44 (0)1223 337356
>> >> Email: djh210_at_cam.ac.uk
>> >> Web: http://www.tcm.phy.cam.ac.uk/~djh210/
>> >>
>> >> ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
>> >>
>> >
>
>

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