Re: ABF:reversibility and number of samples

From: Chris Chipot (Christophe.Chipot_at_edam.uhp-nancy.fr)
Date: Fri May 23 2008 - 10:43:59 CDT

Luca,

> Dear all,
> I used ABF to understand some aspects of
> lingand binding mode.
> A this moment I have a "good" energy profile but
> I do not have an uniform number of samples:I explore along a
> dihedral angle in the range 0-180 and I get to peaks at 20 and about 160 degrees.
> There is a reversibility but sampling is not uniform.
> In particular I have
> a minimun energy that coincide with a minimun sampling.(at 60 degrees)
> I ran my simulation (enzyme+ligand) for about 30ns and
> I can not hope/think that things can change even if increasing
> the simulation length of some tens of ns.
>
> At this point I think about two possibilities:
> 1-Interpretation of these results. Do you guess they can be reliable?
> How can I use them?

The real question here is not the reliability of your results, but
the reliability of your reaction coordinate. We ought to emphasize
again that one of the goals of ABF is to improve sampling along that
reaction coordinate, making the latter as uniform as possible. There
is, however, a stringent assumption being made here: If the reaction
coordinate, which is more than likely a multidimensional one, is
strongly coupled to degrees of freedom in the slow manifolds, sampling
is bound to be nonuniform, at least in the limit of short simulations.

> 2-Split the coordinate to try to reach sampling uniformity within each smaller range.
> For instance: 0-60, 60-120, 120-180.
> Do you have any suggestions ?

It can be shown, indeed, that if convergence of the simulation in a
single window is attained within N steps, splitting the reaction path
into P windows should result, in principle, in a number of steps per
window less or equal than N/P to reach convergence.

Chris Chipot
_______________________________________________________________________

Chris Chipot, Ph.D.
Equipe de dynamique des assemblages membranaires
Unité mixte de recherche CNRS/UHP No 7565
Université Henri Poincaré - Nancy 1 Phone: (33) 3-83-68-40-97
B.P. 239 Fax: (33) 3-83-68-43-87
54506 Vandoeuvre-lès-Nancy Cedex
                             E-mail: Christophe.Chipot_at_edam.uhp-nancy.fr
                                            http://www.edam.uhp-nancy.fr

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_______________________________________________________________________

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