On Wed, 5 Aug 2015, Justin Lemkul wrote:
On 8/5/15 10:32 AM, Smith, Micholas D. wrote:
OPLS-AA 2001 (the one implimented in gromacs) can be a little slow in
folding
(in both my experience, and from doi:10.1016/j.bpj.2009.04.061 ). That is
not necessarily a bad thing if the peptide is suppose to take a while to
fold. If you just want to get to the folded structure, and you don't care
about the pathway, you could also use an enhanced sampling technique.
An alternative force-field that seems to handle beta structures pretty
well,
but can sometime accelerate the folding is the older GROMOS53A force-field;
though since it is united atom, I have found that sometime the contacts
don't
quite match with NMR data.
Beware, it's well known that 53A6 systematically under-stabilizes helices
such that you get inappropriate unfolding. It samples the unfolded state
quite well, but again, this may be application-specific.
That under-stabilization of helices in 53A6 seems to have been mostly
solved by the few changes that led to 54A7, which is able to reproduce
both the thermodynamics and the kinetics of helix formation in a cyclic
peptide model (doi: 10.1021/ct400529k). So, I would say that 54A7 is
largely a "fixed" 53A6 in that respect (plus a few changes on choline
groups and ions).
Of course, the fact that the kinetics seems good is not necessarily a good
thing if you just want thermodynamics (relative populations), because
sampling may turn out to be too slow for your system... or not...
Best,
Antonio
--
Antonio M. Baptista
Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa
Av. da Republica - EAN, 2780-157 Oeiras, Portugal
phone: +351-214469619 email: [email protected]
fax: +351-214411277 WWW: http://www.itqb.unl.pt/~baptista
--------------------------------------------------------------------------
-Justin
Force-field choice is a non-trival, but largely difficult problem to deal
with. In general, though, I tend to avoid the older Amber force-fields when
simulating beta-rich peptides as have had a bias towards helical structures
(see the references within the paper I noted above).
Good Luck,
Micholas
=================== Micholas Dean Smith, PhD. Post-doctoral Research
Associate University of Tennessee/Oak Ridge National Laboratory Center for
Molecular Biophysics
________________________________________ From:
[email protected]
<[email protected]> on behalf of SAPNA
BORAH
<[email protected]> Sent: Wednesday, August 05, 2015 10:20 AM To:
[email protected] Subject: Re: [gmx-users] Force-field bias???
Dear all,
Thank you for your answers which definitely clears some of my doubts. I am
trying to unfold a lectin tetramer protein that comprises largely of beta
strands, and I have used the OPLS ff, so far I have not been successful,
can
OPLS be a problem at all??
Thanks..
Sapna Mayuri Borah c/o Dr. A. N. Jha Research student Tezpur University,
India
On Wed, Aug 5, 2015 at 5:44 PM, Smith, Micholas D. <[email protected]>
wrote:
You should also note that force-field bias may be system dependent. So if
you are unsure of the dynamics from the onset, you should likely test a
variety of force-fields and/or try to find a comparison to NMR (or other)
experimental methods.
-Micholas
=================== Micholas Dean Smith, PhD. Post-doctoral Research
Associate University of Tennessee/Oak Ridge National Laboratory Center for
Molecular Biophysics
________________________________________ From:
[email protected] <
[email protected]> on behalf of Justin
Lemkul <[email protected]> Sent: Wednesday, August 05, 2015 7:31 AM To:
[email protected] Subject: Re: [gmx-users] Force-field bias???
On 8/5/15 6:24 AM, SAPNA BORAH wrote:
Dear all,
I have a general query about unfolding simulations. Is there a bias
among force-fields selected for unfolding, i.e. is it possible that
unfolding
of
the protein may be different with a change in force fields applied?
Literature has given some support on this, however, I am not sure how
this
may happen.
Yes, this is true. It usually comes down to errors in the balance between
intra-protein and protein-water interactions. Incorrect balance favors
either the folded or unfolded state. No force field is perfect, but some
are better than others and there's lots of literature on this topic
regarding which are the most successful.
-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
[email protected] | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul
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==================================================
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
[email protected] | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul
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