Re: binding free energy , binding constant

From: Chris Chipot (
Date: Fri Jun 17 2005 - 11:07:11 CDT

Dear Sabri,

the answer to your question is evidently no. The reason lies
in the incompleteness of your sampling to guarantee that low
energy configurations of the target state are well sampled.
In a matter of general principle, computation of absolute
free energies, as you describe it, is not possible. If you are
interested in a binding free energy, you should think of the
following thermodynamic cycle:

(protein)aq + (ligand)aq ? (protein...ligand)aq

  ?Aannihil,1 ? ? ?Aannihil,2
(protein)aq + "nothing" ? (protein..."nothing")aq

?Aannihil,1 and ?Aannihil,2 are the free energies of annihilation
of the ligand in the free and in the bound states. Alternatively,
you might simply be interested in the relative binding free
energy between two ligands, in which case point mutations will
be performed in lieu of annihilations. Either "alchemical
transformation" can be carried out using the FEP feature of NAMD.

Chris Chipot

sabri bora erdemli wrote:

> Hi,
> I would like to calculate binding free energy and binding constants of
> residues in an interface. I already did simulation with my complex. I
> wonder If I have a chance to calculate them by using output of the
> NAMD simulation. I mean I do not want to make further simulation and I
> think there should be a way to do that, such as an emprical formula
> which includes velocity and coordinate information (which is about the
> interaction with the other residues).
> thank you very much in advance....
> have a nice weekend.....
> Sabri Bora Erdemli
> Research and Teaching Asistant
> Computational Sciences and Engineering
> Koc Universitesi pk.218 34550
> sariyer/Istanbul TURKEY
> tel no: 902123381736
> URL :

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
      To sin by silence when we should protest makes cowards out of men
                                                    Ella Wheeler Wilcox

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