Re: FEP: How check equilibration sufficiency? calculate dG?

From: Chris Chipot (Christophe.Chipot_at_edam.uhp-nancy.fr)
Date: Tue Oct 14 2008 - 04:12:43 CDT

Sebastian,

one simply never calculates absolute free energies, which would
translate to having access to the complete partition function of
the system -- this is never the case in practice. Instead, one
defines a reference system and expresses the Hamiltonian of the
target system as the sum of the reference Hamiltonian and some
perturbation term. The free energy difference between the two
systems can then be expressed as an ensemble average over the
reference system. The latter average can be further expanded in
a series, the first two terms of which are fairly easy to
interpret -- the internal energy and a fluctuation term. Note
that in a number of instances, this second-order interpretation
is enough to understand the physics of the problem. The confusion
between the vocabularies absolute and relative free energies comes
from inappropriate usage of the former when measuring for instance
binding constants or hydration free energies. Even if, in the first
example, one deals with a single ligand bound to a protein, one
still measures a relative quantity -- the difference between a
bound state and a free state.

Chris Chipot

Floris Buelens a écrit :
> Hi Sebastian,
>
> It's not feasible to compute the absolute value of G for a system of any relevant size - you can only realistically sample over small differences dG on the order of kT. To check convergence you're best off monitoring the cumulative dG average which is calculated as your simulation progresses (the last column in the FEP output file).
>
> Best regards,
>
> Floris
>
>
> ----- Original Message ----
> From: Sebastian Stolzenberg <s.stolzenberg_at_gmail.com>
> To: Jerome Henin <jhenin_at_cmm.chem.upenn.edu>
> Cc: namd-l_at_ks.uiuc.edu
> Sent: Tuesday, 14 October, 2008 5:50:43
> Subject: namd-l: FEP: How check equilibration sufficiency? calculate dG?
>
> Dear Jerome,
>
> I would like to to check, if for a step lambda1->lamba2, the FEP
> equilibration time was sufficiently long.
> One criterion I was thinking of was checking convergence of G_1 and G_2
> (corresponding to lambda1 and lambda2 respectively)- are these
> quantities possible to calculate from the FEP output?
> I tried using the energy values, but immediately saw that the numbers
> are so large that they will cause overflow in the exponentials of the
> partition functions.
>
> Is there a special trick to calculate G_1 or G_2? How did you calculate dG?
>
> Thank you,
> Best,
> Sebastian
>
>
>
>
>

-- 
_______________________________________________________________________
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
              The wretch, concentred all in self,
              Living, shall forfeit fair renown,
              And, doubly dying, shall go down
              To the vile dust, from whence he sprung,
              Unwept, unhonored, and unsung.            Sir Walter Scott
_______________________________________________________________________

This archive was generated by hypermail 2.1.6 : Wed Feb 29 2012 - 15:49:58 CST