[gmx-users] Strange problem with simple FEP (bug?)

[David Mobley]

Maik,

> I'm trying to do a simple FEP within a simple protein, which seems to
> make things simple...but as you may expect...it is anything else than that.

> What I'm trying to do is morphing a Tyrosine into a Phenylalanine in OPLSAA.
> Therefore the CZ is changed from the type of TYR to the type of PHE.
> The oxygen(TYR) is changed to a proton(PHE) and the proton(TYR) to a
> dummy (PHE). So this is very simple. We checked the tpr-dump and
> everything looks fine (except, maybe, we missed it). Now, in the
> position-restraint run (where state B should not be regarded by the
> system), the OH-proton moves on top of the OH-oxygen and the simulation
> crashes after a while. We then performed a FEP from TYR to TYR (so A-
> and B-state are the same) and the system runs.

I am not an OPLS guy myself, and I don't know the details of your
transformation, so I'll just tell you one possibility, and you'll have
to decide whether it could apply in your situation.

Sometimes, if you are disappearing a Lennard-Jones site that still has
some amount of electrostatics, it can begin to interpenetrate with
other atoms which either do not have Lennard-Jones interactions
(hydrogens in some force fields) or which do (depending on the
combination rule you use). Obviously, this is bad because (for
example) protons can move on top of oxygens and cause blowing up.

A classic example of this is, for example, if I am turning off the LJ
on an oxygen site at the same time as turning off the charges on that
oxygen. In many FF's, water hydrogens lack LJ interactions, so they
can come and overlap with the oxygen I'm disappearing, which is still
charged (at least to some degree) and cause a "fusion" type event.

I don't know if that's what's going on for you, but you might think
about it -- do you have any atoms that you're disappearing, and are
there other atoms which the combination rules would allow to overlap
with those?

The way I get around this problem in my calculations is to always turn
off electrostatics on any atom I'm disappearing prior to modifying the
LJ parameters, so that I never have a charged atom which is being
treated using the "soft-core" potentials that allow overlap.

Not sure if that's your problem -- just a thought.

David


> The whole thing was done with GROMACS 3.3.1 and TIP4P. Any suggestions?
> Gerrit and me think of a bug somewhere.
>
> Regards
>
> --
> Maik Goette, Dipl. Biol.
> Max Planck Institute for Biophysical Chemistry
> Theoretical & computational biophysics department
> Am Fassberg 11
> 37077 Goettingen
> Germany
> Tel.  : ++49 551 201 2310
> Fax   : ++49 551 201 2302
> Email : mgoette[at]mpi-bpc.mpg.de
>          mgoette2[at]gwdg.de
> WWW   : http://www.mpibpc.gwdg.de/groups/grubmueller/
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