From: Jérôme Hénin (jerome.henin_at_ibpc.fr)
Date: Wed Apr 26 2017 - 05:27:27 CDT
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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