Re: question on ABF

From: Chris Chipot (
Date: Mon Apr 21 2008 - 07:01:39 CDT


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:
> 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
> <> 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
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              And, doubly dying, shall go down
              To the vile dust, from whence he sprung,
              Unwept, unhonored, and unsung.            Sir Walter Scott

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