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
--
==================================================
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
jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul
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