Re: questions regrading ABF

From: Chris Chipot (Christophe.Chipot_at_edam.uhp-nancy.fr)
Date: Tue May 30 2006 - 01:04:28 CDT

Jan:

> Dear Chris,
>
> thanks for your quick answer!
>
>> a) what are the atoms corresponding to abf1 4 and abf2 117 ? Keep
>> in mind that the RC should be decoupled from constrained DOFs.
>
>
> atoms 4 and 117 are the C-alpha atoms of the first and the last residue.
> (In contrast to what I erroneously stated in my previous mail I used
> dodeca-alanine).

If your peptide is shaken/rattled (rigidBonds all), then your
free energy calculation is likely to be erroneous. I would like
to emphasize once again that the RC ought to be fully decoupled
from frozen degrees of freedom. If rigidBonds is set to all, to
allow longer time steps to be used, note that the Calpha...Calpha
RC is coupled to shaken/rattled Calpha-Halpha bonds.

There are three routes you can follow to get the correct answer:

i) turn rigidBonds to none, in which case you can keep the
       Calpha...Calpha RC, but ought to pay attention to the time
       step you are using.

ii) use the distance separating the first and the last carbonyl
      carbon atoms as your RC. These atoms are not coupled to any
      frozen DOF.

iii) keep the Calpha...Calpha as your RC and rigidBonds to all. Turn,
      however, to another type of ABF coordinate: distance-com, and
      include the Halpha in the sets of atoms for abf1 and abf2.
      Literally, your RC will be the distance separating the COMs
      of the first and the last Calpha-Halpha bonds, which is close
      enough to a true Calpha...Calpha distance.

>> b) note that the free energy minimum of the alpha-helix emerges
>> around 14 angstroms. In your input file, xiMin is 18.
>
>
> I just started with the folded helix where the distance between the
> atoms is about 18 A (for dodeca-alanine; meanwhile I tried the same with
> deca-alanine and got the same bad sampling). The goal was to unfold the
> helix starting from the perfectly olded state.

See answer to point a). I can guarantee that your sampling will improve
instantly if you respect the above basic requirements for running ABF
free energy calculations. In a matter of 2 ns, you should get a very
reasonable estimate of the stretching free energy profile.

>> c) the role of dxi is important and should be chosen as a function
>> of how rapidly the free energy is changing. 0.5 angstroms is in
>> the case of deca-alanine probably too large. 0.1-0.2 angstroms
>> is typically what we used. dSmooth should set accordingly.
>
>
> I tried values between 0.5 and 0.02. The potential form changes but the
> sampling is equally bad in all cases.

See answer to point a). Pick either i), ii) or iii) and switch to a
0.1-0.2-angstrom dxi. Update dSmooth accordingly, ca. 0-0.2. In the
gas phase, the threshold for applying the average force, FullSamples,
can be set to a rather low value, viz. typically 100 samples.

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 Vand½uvre-lès-Nancy Cedex

                             E-mail: Christophe.Chipot_at_edam.uhp-nancy.fr
                                            http://www.edam.uhp-nancy.fr

     Science without management is worse than management without science

                                                        N. G. van Kampen
_______________________________________________________________________

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