Re: AMBER: FEP error/early termination - why?

From: Carlos Simmerling <>
Date: Mon, 31 May 2004 14:21:41 -0400

oh, I see. I thought it was the same person, sorry...

I think it is always a good test to remove the charge
on the atoms before disappearing the vdw if
you are having problems with convergence or stability.
when removing hydroxyl groups, this is very
important since making the oxygen "smaller" can
leave the hydrogens (that have no vdw term)
as exposed charges. your case is probably simple
enough that decoupling may not be needed.
if you aren't having problems, I don't think you
should worry about decoupling.


  ----- Original Message -----
  From: Sébastien Osborne
  Sent: Monday, May 31, 2004 2:12 PM
  Subject: Re: AMBER: FEP error/early termination - why?

  sorry for confusion... different person... different simulation... I am doing asn --> asp and the other persone was doing another.

  Carlos Simmerling wrote:

    you originally said you tried asp-->ala, that is why dac mentioned decoupling.
    now you say you are doing asn-->asp. which is right?
    also, since you are removing a formal charge, it is not at
    all surprising that your free energy curve differs from val-->ala
    where the only change is really size.
      ----- Original Message -----
      From: Sébastien Osborne
      Sent: Monday, May 31, 2004 1:51 PM
      Subject: Re: AMBER: FEP error/early termination - why?

      what exactly do you mean by "decoupling the charge change and the VDW change"? I am trying to do the following perturbation: ASN --> ASP where the NH2 part of ASN becomes O. In the process, I am perturbing the hydrogen atoms to dummy atoms. Are you saying it is better to perform 2 runs, a first run where the hydrogen becomes "charged" dummy atoms (no change on the charge in the run) followed by a second run where the charge on the dummy atoms become 0?

      Thanks for the help.

      Sebastien Osborne
      University of Ottawa

      David A. Case wrote:

On Mon, May 31, 2004, Annette Höglund wrote:
  I have tried to run an initial free energy perturbation for a ASP->ALA
sidechain in a protein-DNA complex (after minimization and
equilibration) using a similar gibbs input as in the val-to-ala tutorial.
For this particular sidechain the FEP terminates after about 75% with
When I plot the F_energy it seems to be a "concave" rather than "convex"
curve (as in the tutorial).
Are you decoupling the charge change from the van der Waals change? (Not
doing that _could_ lead the symptom you cite, but that is just a guess.) Be
sure to run the ASP->ALA change in water first (since it is simpler, and can
help you debug your scripts), before trying it in the protein/DNA system.

....good luck...dac

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Received on Mon May 31 2004 - 19:53:01 PDT
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