[gmx-developers] possible interplay between intermolecular restraints and parallelization?

[David Mobley]

Dear Devs,

For many years we have been doing binding free energy calculations with
restraints to hold the ligand in the binding site. Lately, however, as we
move to bigger systems, we simply can't get these simulations to run
stably. Does anyone have experience with using restraints between
relatively distant atoms in parallel simulations? Any encounters with
similar problems or suggestions?

Specifically, we normally use a set of six restraints between the ligand
and the protein to restrain the six rigid-body degrees of freedom. These
use three reference atoms in the protein and three in the ligand, as
described in the reference below. Normally these atoms are relatively
distant from one another, by design.

We have in the past mostly used distance_restraints, angle_restraints and
dihedral_restraints for implementing these. However, these seem to lead to
stability problems when we run on a few cores (perhaps 8) as we move to
larger systems, and especially so when using constraints on bonds involving
hydrogen. Additionally, since these restraints cannot be applied between
'molecules' in the topology, this means there are technical reasons we
prefer another form for the restraints.

Lately, we have been testing using special bonds, angles, and dihedrals for
restraints between these atoms. However, we keep encountering stability
problems there as well, at least when running in parallel (we are testing
whether running on a single core will alleviate these). We DO already know
that if we take a topology file which will run stably in serial with the
old form of restraints, convert the restraints to the new form (bonds,
angles, dihedrals) and attempt to run it in parallel we tend to run into
problems.

In any case, does anyone have experience with using restraints between
relatively distant atoms, and suggestions on how to get our systems to run
stably? For what it's worth, these are systems which run fine in parallel
without the restraints, and the restraints are not unusually strong. (We've
run with stronger restraints many times in the past without issues).

Thanks!

Reference:
http://dx.doi.org/10.1021/jp0217839


-- 
David Mobley
dmobley at gmail.com
949-385-2436
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