[gmx-users] free energy calculations blowing up

[David Mobley]

Jonathan,

Two comments:
(1) Although this wasn't your question, you might not want to run the
simulations sequentially. I think previous work has shown that you can
introduce some hysteresis this way, although the reference eludes me at the
moment.
(2) When changing vdW parameters, soft core helps a lot. From what you're
describing it sounds like you are doing that. If you don't use soft core,
dV/dlambda actually has a singularity for particle insertion as lambda->1
(assuming the exponent of lambda is 1, which it is by default) and is also
very susceptible to shot-type noise, and susceptible to crashes when forces
get too large (which often happens near lambda=1). You can reduce the
crashes somewhat by using smaller timesteps but this doesn't help with the
shot noise or singularity problems. To understand why this happens you can
look up van Gunsteren's paper from around 1992 introducing the soft core
potential, or contact me directly for a brief explanation. If you have any
trouble finding the reference I can look it up for you, but I don't have it
in front of me right this instant.

David Mobley
UCSF



On 11/11/05, Moore, Jonathan (J) <JMoore2 at dow.com> wrote:
>
>
> I have a question about free energy calculations.
>
> I'm performing several different simulations where the hydrogen of certain
> hydroxyls on my molecule is replaced with a methyl group. It's a united atom
> model, so the change from hydrogen to methyl doesn't change the number of
> sites. I have a single molecule of interest in SPC water (see more details
> below). I'm experiencing the problem that on occasion the system blows up.
> I've had no problems like this previously when simulating only one state or
> the other (methylated or unmethylated), so I think the problem is due to the
> free energy calculation. Unless I've made an error in setting up the free
> energy calculation, I assume my problem is that the system isn't stable for
> the timestep that I'm using (2 fs) and how fast I'm changing lambda (I'm
> incrementing lambda by 0.05 followed by 200 ps of simulation before
> increasing it again).
>
> Is it common to either decrease the time step or use lambda increments
> smaller than 0.05 when doing free energy calculations this way? I'm
> planning to try both to see if they fix the problem, but I'm curious if
> anyone else has had a problem like this. I'm not using soft cores, but maybe
> I have to?
>
> Also, I'm specifying the atom types like this (i.e., with the mass being
> taken from the .atp file):
>
> [ atoms ]
> ; nr type resnr residu atom cgnr charge
> 6 H 1 H000 HO3 2 0.410
>
> Therefore, when I specify the B state, I do it like this (i.e. with out
> specifying the change in mass, assuming the GROMACS will also get the B
> state mass properly from the .atp file):
>
> [ atoms ]
> ; nr type resnr residu atom cgnr charge
> 6 H 1 H000 HO3 2 0.410 CH3 0.180
>
> Should that work OK? It wasn't obvious to me where to look in the output
> to make sure it is. I assume I'll be able to answer that question myself
> when 3.3.1 is released and I can use "gmxcheck -ab"
>
> More details:
> v. 3.2.1, single precision
> 2 fs timestep
> All bond lengths constrained (LINCS)
> Nosé-Hoover thermostat with the polymer and solvent coupled separately;
> 0.4 ps time constant
> Berendsen barostat with 0.5 ps time constant and 4.5x10-5 bar -1
> compressibility
> Triple-range cut-off method
>
> Thanks,
> Jonathan
>
> ____________________________
> Jonathan Moore, Ph.D.
> Research and Engineering Sciences - New Products
> Core R&D
> The Dow Chemical Company
> 1702 Building, Office 4E
> Midland, MI 48674 USA
> Phone: (989) 636-9765
> Fax: (989) 636-4019
> E Mail: jmoore2 at dow.com
>
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