Re: ABF:reversibility and number of samples

From: Luca (bellucci14_at_unisi.it)
Date: Fri May 23 2008 - 14:26:03 CDT

 Chris, Jerome, Thanks for your help.
I used ligand dihedral angle to explore a binding site of one enzyme,
therefore I agree with assumptions that the reaction
coordinate is strongly coupled to low degrees of freedom.
Accordingly with this, observed "reversibility/irreversibility" could depend on many random
low degrees of freedom.
In order to reduce this effect I can restraint the protein (backbone for example).
Whit this, I can check the real reversibility/irreversibility of the "original" system.
Thanks
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
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> E-mail: Christophe.Chipot_at_edam.uhp-nancy.fr
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>
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