AMBER Archive (2004)

Subject: AMBER: positive binding free energy

From: hj zou (
Date: Wed Mar 10 2004 - 00:43:58 CST

Dear amber usersúČ
  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 usersúČ
> 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

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