From: L. Michel Espinoza-Fonseca (mef_at_ddt.biochem.umn.edu)
Date: Mon May 05 2008 - 09:16:44 CDT
Jerome, Chris,
Thank you very much for your comments on this issue. After thinking a
little bit more about my specific system and considering your
comments, I'm afraid that ABF won't be the method of choice for the
problem I want to tackle. The main issue here will be the
conformational sampling of the interface of the dimer (there is a long
loop present at the interface); even if I can perform a test run, I'm
sure I'll face serious undersampling problems.
In any case, thank you very much for the insightful comments!
Cheers,
Michel
On Mon, Apr 21, 2008 at 2:01 PM, Chris Chipot
<Christophe.Chipot_at_edam.uhp-nancy.fr> wrote:
> Michel,
>
>
> I would also add to Jerome's comments that what we perceive as the
> free energy minimum in reality corresponds to an ensemble of states
> where the two helical segments are in contact. Yet, these states can
> be distinguished by minute differences in the interdigitation of the
> participating side chains. They can also be distinguished by the
> rotation about the longitudinal axis of the helices. Converged
> configurational ensembles at constant xi imposes that these states,
> corresponding to distinct intrinsic rotations of the helices and
> interdigitations of their side chains, be properly sampled, which,
> in the case of large proteins can be overwhelming.
>
>
> Chris Chipot
>
>
> Jerome Henin wrote :
>
>
>
> > Hi Michel,
> >
> > I don't know if you have read this previous thread:
> > http://www.ks.uiuc.edu/Research/namd/mailing_list/namd-l/6992.html
> >
> > To elaborate on this, I would recommend that you estimate which
> > degrees of freedom (including protein conformation and overall
> > rotation) will be involved in the calculation (i.e. will need to relax
> > and be sampled).
> >
> > For comparison with the case of GpA discussed in the previous thread,
> > I would remember that:
> > 1) the system was only the GpA TM segment, much, much smaller than
> > what you consider;
> > 2) the environment imposed a TM orientation, introducing strong
> > orientational restraints;
> > [3) note that we used an alkane medium instead of actual lipids, for
> > faster relaxation]
> >
> > One relevant question to ask at this stage is: which degrees of
> > freedom should absolutely be sampled? (and the flip side, what could
> > you possibly get away with not sampling, and can be restrained...).
> > For a system of this size, I would add: would you get any information
> > by looking at something smaller first?
> >
> > Cheers,
> > Jerome
> >
> >
> > On Fri, Apr 18, 2008 at 7:40 PM, L. Michel Espinoza-Fonseca
> > <mef_at_ddt.biochem.umn.edu> wrote:
> >
> > > Dear all,
> > >
> > > I was wondering if you any of you (that question is particularly meant
> > > for Jerome) have used ABF to calculate the unbinding free energy of
> > > two proteins. I have a homodimer, with each monomer consisting of ~250
> > > residues; the reaction coordinate will be defined as the distance
> > > between the COM between each monomer.
> > >
> > > Cheers,
> > > Michel
> > >
> > >
> > >
> >
> >
> >
>
> --
> _______________________________________________________________________
>
> 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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> Living, shall forfeit fair renown,
> And, doubly dying, shall go down
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> _______________________________________________________________________
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