[gmx-users] Why not PBC for implicit solvent?

[Justin Lemkul]

On 2/26/13 9:23 AM, Sebastien Cote wrote:
> Dear Justin (and Yun),
>
> Since our last discussion on implicit solvent simulations, I have read a bit more about how cutoffs in GBSA (or variants) implicit solvent simulations are used in other softwares such as AMBER, CHARMM and NAMD.
> It appears to me that many use switch or shift cutoffs. Have you tried this in your tests? Such boundary conditions should remove any non-conservation of energy problem. As you said, protein stability should also be tested though.

I haven't tested switching or shifting.  In a theoretical sense, that would make 
a lot of sense.  My issues were practical, though.  My implicit solvent 
experience is all in the 4.5.x series of Gromacs, where one could use OpenMM 
acceleration for GPU.  I found a lot of features were unsupported (like 
switching and shifting) and/or unreliable (systems crashing).  So I gave up on 
OpenMM for GPU and moved to CPU, where I encountered a bug that prevents use of 
more than 2 CPU for running MD (which still exists).  Since I was relegated to 
only 1 or 2 processors for these runs, I tried to get the maximum performance 
while still maintaining accuracy.  Switching and shifting were obviously slower 
than cutoffs, and as I said before, finite cutoffs were terrible.  I decided on 
exclusive use of infinite cutoffs due to the fact that they were (1) more stable 
and (2) allowed the use of the accelerated all-vs-all kernels, which helped 
performance.

Please note that none of the above applies to the native GPU acceleration in 
Gromacs 4.6, but the bug limiting implicit solvent simulations to 1 or 2 CPU 
still exists.  The present GPU acceleration also does not support implicit 
solvent simulations, IIRC.  I have not needed to test it yet, though.

> Moreover, many use a non-zero salt concentration giving rise to a Debye screening (exp(-r*kappa), kappa^-1 ~ 1 nm under physiological concentration). Such screening makes the electrostatic energy tends to zero faster. In GROMACS, it is possible to specify a salt concentration for the implicit solvent scheme in the .mdp file, but such variable has not been coded for in the source code (as explained in the manual). From what I saw, this is still on the to-do list of the developers. Is it still under development?

Theoretically, but I've not seen any movement on that issue.  I will file a 
request on redmine.gromacs.org.  Anything not filed there typically gets lost in 
the development process, so if there are things people want to see implemented, 
they need to be filed.

> Finally, there as been a post on the Gromacs mailing list late 2012 about some energy differences between the AMBER and GROMACS implementation of OBC GBSA. It was found that the parameters of the gbsa.itp file should be changed to obtain a better energy agreement for the GB part. The SA part also showed some energy difference that could not be corrected for and were attributed to different surface accessible calculation algorithm. See : http://lists.gromacs.org/pipermail/gmx-users/2012-November/076230.html.

Probably a worthwhile improvement.  I'll file that on Redmine as well.

-Justin

>> Date: Tue, 26 Feb 2013 06:56:40 -0500
>> From: jalemkul at vt.edu
>> To: gmx-users at gromacs.org
>> Subject: Re: [gmx-users] Why not PBC for implicit solvent?
>>
>>
>>
>> On 2/25/13 10:30 PM, Yun Shi wrote:
>>> Hi everyone,
>>>
>>> Previous posts mentioned setting pbc = none for MD simulations with
>>> implicit solvent. But I am trying to see the behavior of certain
>>> concentration of ligands (small molecules, no big biomolecules) in
>>> solvent, so I wonder if setting pbc = xyz would cause any problem for
>>> my system?
>>>
>>
>> I see no theoretical problem with running NVT with "pbc = xyz" with implicit
>> solvent, but definitely not NPT since the box will shrink inwards and lead to
>> periodicity artifacts (if it even remains stable at all).  I usually set a
>> nonperiodic box because it allows me to use the infinite cutoff approach, which
>> is the only one I have found to give sensible results.
>>
>>> Should I also stay with the normal cutoff values for vdw and coul interactions?
>>>
>>
>> Maybe, but do some serious testing before relying on the results.  Maybe for
>> small molecules a finite cutoff will work, but for proteins I have tried cutoffs
>> of 1.0, 2.0, 4.0, and even 8.0 nm and all have unfolded or distorted.
>>
>> -Justin
>>
>> --
>> ========================================
>>
>> Justin A. Lemkul, Ph.D.
>> Research Scientist
>> Department of Biochemistry
>> Virginia Tech
>> Blacksburg, VA
>> jalemkul[at]vt.edu | (540) 231-9080
>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>>
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-- 
========================================

Justin A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================