I’ve conducted several 100ns MD simulations on the same small protein receptor using different non-polar ligands. The results obtained were quite consistent. When I used a ligand with a polar group (de-protonated carboxylate moiety) the ligand flies out of the binding pocket after a few nanoseconds simulation.
Two separate MD runs were conducted. The simulations were started with the ligand in antiparallel poses (polar groups at 180• from each other). Ligand poses were obtained from docking simulations (AutoDock).
In both cases the ligand was equilibrated for 2ns (all restraints removed) after which MD production was initiated. The ligand appears to gradually move out of the binding pocket during the equilibration MD (Run 1) and during the first 5 ns of the MD production in Run2. The exit gates are different in each case.
There is biological evidence that the ligand binds on the receptor.
Any suggestions regarding this behavior would be most welcome.
Regards
George
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Received on Mon Sep 08 2014 - 13:30:02 PDT
