[gmx-users] pressure and temperature coupling is off in vacuum simulations

[Erik Marklund]

> On 23 Sep 2015, at 12:35, Justin Lemkul <jalemkul at vt.edu> wrote:
> 
> 
> 
> On 9/23/15 6:37 AM, Erik Marklund wrote:
>> 
>> On 23 Sep 2015, at 08:28, Mark Abraham
>> <mark.j.abraham at gmail.com<mailto:mark.j.abraham at gmail.com>> wrote:
>> 
>> Hi,
>> 
>> On Wed, Sep 23, 2015 at 8:32 AM tasneem kausar
>> <tasneemkausar12 at gmail.com<mailto:tasneemkausar12 at gmail.com>> wrote:
>> 
>> Dear Gromacs users
>> 
>> I have performed MD simulation for protein in vacuum condition.
>> 
>> 
>> That's super artificial, so nothing else you do matters :-)
>> 
>> This tongue-in-cheek reply does deserve a comment. Indeed the vacuum
>> conditions introduce additional accuracy problems to the physical model, and
>> one must be aware of this as to not over-interpret the results. A very fair
>> point. That is not to say that we cannot learn from vacuum simulations of
>> macromolecules however. Surely, the approach to, for instance, treat the
>> protein as perfect ball also suffers from accuracy problems?! Or do you
>> object to the notion of gas-phase proteins are artificial? Sure, it rarely
>> happens in cellular processes (to my knowledge), but mass spectrometry is an
>> extremely useful technique for the biosciences and requires gas-phase
>> samples. As such experiments become more advanced (and they do, rapidly),
>> there are more and more reasons to model the experiments. We do not know the
>> objective here, and should not be so quick to dismiss the investigation.
>> 
> 
> Erik, perhaps you can comment on an issue I've wondered about: to what extent do any of the force fields available in GROMACS prove useful in the gas phase? They are all designed for condensed phase systems, and are parametrized to reproduce behavior in/interactions with water.  The intrinsically overestimated dipoles (required for the additive approximation) would yield interactions in vacuo that are generally much too strong, or incorrect altogether.  I'd be curious to get your opinion on this.
> 

Well this is the main problem, and one reason for exploring polarisable models instead of non-polarisable ones. The surface of the protein will be over-polarised with current force fields, but I would expect the interior to suffer much less from this effect. Still, the surface sure is important.

One example where gas-phase simulations have been useful for us is when we monitor the gas-phase unfolding under varying degree of collisional activation using ion mobility spectrometry (IMS). The simulations can indicate roughly what degree of unfolding give rise to the observed shifts in the IMS spectrum. IMS data contains structural information, but extracting the latter requires modelling, and MD has been helpful. That said, the various inaccuracies in the physical model precludes quantitative conclusions on the level you would expect to be able to draw from solution phase simulations.

Erik


> -Justin
> 
> -- 
> ==================================================
> 
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
> 
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
> 
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
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