[gmx-users] temperature variation of all-atom CHARMM force fields

Justin Lemkul jalemkul at vt.edu
Thu Jul 2 17:28:46 CEST 2015

On 7/2/15 10:33 AM, soumadwip ghosh wrote:
> Hi,
>      I am stuck with one of the reviews of my paper where i have
> investigated the thermodynamics of small molecular ion binding to DNA
> duplex using CHARMM 27 force field. In order to do so I calculated the PMF
> of the binding processes at different temperature ( 300, 270 and 330K) and
> then decomposed the temperature dependent PMFs to estimate the entropy and
> enthalpy contributions respectively. One of the reviewer has strong
> objection about the validation of classical force fields beyond room
> temperature. While I know this has been a major issue in simulation of
> biomolecules (say temperature assisted protein unfolding or hydrophobic
> interactions between two methane molecules in water) and REMD may be a
> possible way out but there are examples of works such as below where
> temperature variation of force fields during a classical MD simulation did
> not seem to be an issue or neither has been addressed by the authors.
> http://pubs.acs.org/doi/pdf/10.1021/jp056909r
>   and
> http://pubs.acs.org/doi/pdf/10.1021/jp512336n
> I cannot perform REMD for all the ion associations at this moment and apart
> from this comment I have satisfactorily answered the rest of the queries of
> the referees. Is there some way by which I can convince the referee? Can
> anyone help me with some references where CHARMM force fields have been
> used without any modification to study a biomolecule beyond room
> temperature using MD simulations? In general I will be highly obliged if
> someone helps me with an appropriate response to the reviewer?

There have been DNA base flipping studies that have done this, though I don't 
remember if it was with CHARMM or AMBER.  In any case, an objection about 330 K 
strikes me as pretty absurd.  That's not an unreasonable temperature, and people 
simulate membrane proteins in DPPC at 323 K or higher all the time and they're 
fine.  You start getting into trouble at 400, 500 K, etc.



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


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