AMBER Archive (2006)

Subject: Re: AMBER: error estimate for free energy perturbation calculation

From: Ilyas Yildirim (yildirim_at_pas.rochester.edu)
Date: Wed Oct 25 2006 - 18:17:36 CDT


Dear Jeny,

One method u can use is Block Averaging method. It is a general approach
used to get error estimates. If you google on this method, I am sure u
will get the basics of it. (Its pretty simple) Good luck.

Best,

On Wed, 25 Oct 2006, Chris Moth wrote:

> jz7_at_duke.edu wrote:
>
> > Dear all,
> >
> > Can someone please recommend references for the estimate of error
> > (including sampling error) for the free energy perturbation calculation?
> > I want to know how reliable my delt_delt_G is, and how many trajectories
> > are necessary, how small each step should be, etc.
> >
> > Thanks so much!
> >
> > Jeny
>
>
> Ths is a question of great question to me, as well. I hope you get a lot
> of answers.
>
> There is some discussion of this in Leach's, "Molecular Modelling
> Principles and Applications" Section 11.6 "Potential Pitfalls with Free
> Energy Calculations", along with important caveats.
>
> This recent article was interesting to me: "Free energy perturbation
> approach to the critical assessment of selective cyclooxygenase-2
> inhibitors"
> Journal of Computer-Aided Molecular Design 19: 1731, 2005
>
> and it states
>
> "Starting from the equilibrated structures obtained from the
> aforementioned procedure, we performed the production dynamics of
> perturbation
> for COX-2 in complex with the inhibitors shown in Figure 3. Each
> perturbation consisted of
> 21 windows with 5000 steps of equilibration and 10,000 steps of data
> collection. ..... The free energies reported in the remainder of this
> paper always refer to the forward direction, i.e., in the direction from
> k 0 to k 1. As an estimation of the statistical error, we used half
> the difference between the absolute values of
> forward and reverse free energy changes, and the error in DDGbind is
> calculated as the square root of the sum of the squares of the
> individual errors in
> DGunbound and DGbound. "
>
> In my own experimentation with FEP, I found I could get acceptably small
> error increases (~.1kCal or so) with larger lambda steps in the middle
> points of the trajectory. delta-Lambda need not be constant. I suppose a
> lot could depend on one's particular system.
>
> I found it interesting that the above authors got dGdG binding errors
> less than .8 kCal/mol - but I am also thinking that perhaps their
> equilibration and data gathering runs might have been a bit on the short
> side (see Leach).
>
> Chris
>
>
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-- 
  Ilyas Yildirim
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