RE: AMBER: positive binding free energy

From: Yong Duan <>
Date: Wed, 10 Mar 2004 10:47:37 -0500

This is possible. I am not sure that Docking was the step that lead to
the problem. Nevertheless, we might be more helpful if you can provide
a bit more detailed information, like how did you do the simulations,
the main features of the ligand and protein, the typical values of the
individual energy terms (and the uncertainty of them).

I doubt methods like MM/PBSA is this sensitive to the specifics of a
force field, assuming you did the right thing for ligands. By the way,
how did you obtain the ligand model? We are typically very shy on
questions like "My results are wrong. Please help me to get it right."


> -----Original Message-----
> From:
> [] On Behalf Of hj zou
> Sent: Wednesday, March 10, 2004 1:44 AM
> To:
> Subject: AMBER: positive binding free energy
> Dear amber users,
> Thanks a lot,Dr. Holger.
> As suggested by Dr. Holger,I have tried sevaral docked
> structures.Unfortunately,all of the total binding free
> energies were positive.Someone told me that amber forcefield
> sometimes does not deal with the small molecule well.Is that
> a good explanation?
> If the docked structure is not appropriate,how can I get
> the complex structure(I have tried Dock,Autodock and
> Flexx).Any other methods?
> Any suggestions are appreciated.
> Best regards
> >
> > 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?
> Holger:
> >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
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Received on Wed Mar 10 2004 - 16:53:00 PST
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