[AMBER] docking evaluation using amber

From: erik zuiderweg <zuiderwe.umich.edu>
Date: Fri, 11 Mar 2011 20:33:00 -0500

We have docked a ligand to a protein using AUTODOCK 4.2.
We use a protein structure that is minimized and equilibrated to 300K in Amber.
AUTODOCK gives many docks that are structurally very different but "energetically" the similar.

We want to evaluate the results using Amber 11.

We put the ligand where it belongs according to AUTODOCK, use Antechamber, tleap to get it going, and all is well.
Minimize, equilibrate to 300 K using restraints to keep everything inplace, then run MD without restraints on the ligand. Using GB.
The ligand dissociates now in a few 10's of pico seconds.

Experimental off-rate is 10 s-1.

(a) do I confuse microscopic and macroscopic kinetics?
(b) should I not worry about the time scale problem, and just compare "fly-off" rates to rank my different docks?
(c) Is the problem in using Generalized Born -- should I use explicit solvent?


Erik R.P. Zuiderweg
Professor of Biological Chemistry
University of Michigan Medical School
1150 W. Medical Center Drive
Ann Arbor MI 48109-0600
Office Phone (734) 615 6365
Cell Phone (734) 276 4463
Lab Phone (734) 615 6378

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Received on Fri Mar 11 2011 - 18:00:02 PST
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