AMBER Archive (2004)

Subject: Re: AMBER: positive binding free energy

From: Holger Gohlke (gohlke_at_bioinformatik.uni-frankfurt.de)
Date: Fri Mar 05 2004 - 02:30:35 CST

hj zou schrieb:
>
> Dear amber users£¬
> I'm performing mm-pbsa and nmode calcultion on a docked protein-ligand complex.
> The mm-pbsa result:PBTOT=-13.50,The nmode result:TSTOT=-23.45.So the binding free energy is a positive value.That's impossible.The ligand binds to the protein with a Kd of 47.3nM(experimental measurements). Why?
> Can anyone give me some suggestions?

Considering that several large terms add up to a usually small binding
free energy, it is very hard to tell what might have gone wrong here.
Since you write below that a crystal structure has worked but your
docked complex hasn't, a first guess might be that your ligand binding
mode obtained by docking isn't the appropriate one?!

Best regards

Holger

> (By the way,I also calculated the binding free energy of another complex which has crystal structure in which another liand bound to the same protein. The calculated results were consistent with the experimental data well.)
> Thanks a lot.
> best regards
>
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-- 
++++++++++++++++++++++++++++++++++++++++++++++++++
Dr. Holger Gohlke

J.W. Goethe-Universität
Fachbereich Biologie und Informatik
Institut für Mikrobiologie	
Marie-Curie-Str. 9              
60439 Frankfurt/Main            
Germany                         

Tel.:  (+49) 69-798-29503; Fax: (+49) 69-798-29826
Email: gohlke_at_bioinformatik.uni-frankfurt.de
URL:   http://www.rz.uni-frankfurt.de/~hgohlke
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