On 18/10/2011 4:58 AM, Ben Reynwar wrote:
On Fri, Oct 14, 2011 at 9:11 AM, Mark Abraham<mark.abra...@anu.edu.au> wrote:
On 14/10/2011 10:12 AM, Ben Reynwar wrote:
Hi gromacs list,
I'm about to start some REMD simulations using generalized Born
solvent on a protein of about 5000 atoms. I have two questions, the
first of which is about gromacs, the second more about REMD in
general.
(1)
I'm getting some pretty ugly energy drift (300K->500K in 1 ns) for an
NVE MD test simulation using a 2 fs time step. It goes away if I use
1 fs, however I was under the impression that 2 fs is normally OK. I
was wondering whether that could be caused by the use of the cut-off
method which is required with the coloumb and VdW interactions when
using GBSA? Or perhaps I'm doing something else wrong. I'll include
the mdp file I'm using at the bottom of the email in case anyone feels
like pointing out my foolishness to me.
Drift is normal if you use 2fs with hbond constraints. all-bond constraints
are necessary for 2fs.
Great. Thank you.
(2)
I've been analyzing some data from an REMD simulation by my
predecessor and see very slow replica flow rates. They are about two
orders of magnitude smaller than the idealized rate of the exchange
attempt frequency multiplied by the acceptance fraction (exchanges are
attempted every 2 ps with a 0.4 acceptance fraction). If I look at
the energy distribution for a given replica/temperature combination
over a time scale of around 1 ns, it is clearly shifted from the
average energy distribution for that temperature. The timescale for
changes in this energy shift is around 10 ns. My current theory for
the slow rate of replica flow is that the slow fluctuations in the
energy of the protein are limiting replica flow, since a replica with
lower than average energy will tend to remain at the bottom of the
temperature range, while those with higher than average energies will
tend to remain at the top. Has anyone else observed this kind of
behavior? Is my reasoning wrong in any obvious way?
A replica with "lower than average energy" *for that temperature* will tend
to drift down the temperature ladder in favour of another.
One can observe blockages in replica flow. If all the replicas below a given
temperature are in regions of configuration space that cannot access PE high
enough to have a significant chance of exchanging above that temperature,
then flow does not occur (and vice-versa, of course). If one were to sample
a FES that had two minima that should be sampled in a 2:1 ratio, but started
from a 1:1 ratio and did not have a high enough temperature range to cross
the barrier, then the exchange acceptance rate can look good when nothing
useful is occurring - the observation will necessarily be that these minima
are equally likely. The two groups are actually engaging in disjoint flow,
and one needs to look at metrics other than the acceptance rate to observe
it. The only way to deal with such a bottleneck is to have replicas at a
high enough temperature that both groups can exchange to those temperatures
- only now can barrier crossing occur. These kinds of phenomena can
certainly occur over short time scales in localized regions of configuration
and temperature space.
Mark
Do you know if anyone has done any studies looking at replica flow in
well-defined, comparatively low-dimensional landscapes to get a
qualitative feel for these kinds of effects? It would be interesting
to see what effect replica exchange settings can have on replica flow
beyond the simple random walk models, when you take into account the
fact that different regions of configuration space could have
different potential energy distributions for the same temperature.
See for example Walter Nadler, Jan H. Meinke, and Ulrich H. E. Hansmann
"Folding proteins by first-passage-times-optimized replica exchange",
PHYSICAL REVIEW E 78, 061905, 2008 (and related work)
Mark
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