Re: [AMBER] best Generalized Born solvation model for intrinsically disordered peptides

From: Thomas Evangelidis <tevang3.gmail.com>
Date: Thu, 5 Sep 2013 18:36:58 +0300

Hi,

I have run 4 explicit solvent aMD simulation (99SB-NMR1-ILDN & TIP4P-Ew) of
an IDP with 2 disordered tails, starting from extended tail conformations.
Each one was for 250 ns. In all conformations the first tail remained
disordered with some helical turns, whereas the second adopted a helical
conformation near the end of the simulation. In contrast during aMD
simulations with igb 8 both disordered tails formed perfect helices and
remained like that no matter how long the simulation was. Hence I'm pretty
sure that, at least in my cases, igb 8 overestimates the helical content of
the ID proteins/peptides.

~Thomas

PS: I never said I ran just 17 ns of cMD in implicit solvent. What I said
was that igb 8 folds the peptide to an alpha-helix after ~17 ns. The total
simulation time was much longer.


On 5 September 2013 17:48, Daniel Roe <daniel.r.roe.gmail.com> wrote:

> Hi,
>
> On Tue, Sep 3, 2013 at 2:55 PM, Hai Nguyen <nhai.qn.gmail.com> wrote:
> > how long you have been running? 20ns? if yes, I suggest to run much
> longer
> > like microsecond. For a small peptide, getting this long simulation isn't
>
> Just to expand on Hai's point a bit, one of the major issues when
> comparing implicit solvent to explicit solvent runs is that in
> explicit solvent, conformational sampling is typically much slower
> than in implicit solvent (due to friction, explicit solvent
> rearrangement, etc). You haven't said how long the explicit solvent
> runs are, but you need to be sure that the structural properties in
> each simulation are reasonably converged before you compare them, and
> if you've only run explicit solvent as much as your implicit (17 ns)
> chances are the run is not converged.
>
> > the parameters quoted at the end of the message. In contrast, when using
> > igb 7 the peptide has some helical propensity but is mostly
> > unstructured (helical and random coil conformations are in equilibrium).
>
> This result may not necessarily be wrong, but as Carlos said the GB
> neck (igb=7) model has a tendency to destabilize hydrogen bonding so
> be wary of these results. For more on this see:
>
> Roe, D.R.; Okur, A.; Wickstrom, L.; Hornak, V.; Simmerling, C., J.
> Phys. Chem. B, 2007, 111, 18461857.
> Shell, M.S.; Ritterson, R.; Dill, K.A., J. Phys. Chem. B., 2008, 112,
> 6878-6886.
>
> -Dan
>
> --
> -------------------------
> Daniel R. Roe, PhD
> Department of Medicinal Chemistry
> University of Utah
> 30 South 2000 East, Room 201
> Salt Lake City, UT 84112-5820
> http://home.chpc.utah.edu/~cheatham/
> (801) 587-9652
> (801) 585-9119 (Fax)
>
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> http://lists.ambermd.org/mailman/listinfo/amber
>



-- 
======================================================================
Thomas Evangelidis
PhD student
University of Athens
Faculty of Pharmacy
Department of Pharmaceutical Chemistry
Panepistimioupoli-Zografou
157 71 Athens
GREECE
email: tevang.pharm.uoa.gr
          tevang3.gmail.com
website: https://sites.google.com/site/thomasevangelidishomepage/
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Received on Thu Sep 05 2013 - 09:00:02 PDT
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