Dear AMBER users,
I am currently using MD and MM/PBSA to investigate the binding modes and
energies of small ligands ("fragments" with MW <250 Da) binding in the
active site of my target enzyme. *The binding pocket is solvent exposed and
relatively small. And the ligands are relatively small with weak binding
affinities. *After ~500 ps equilibrium, I ran 8 ns MD. Between 1-2 ns of
production phase, I observed the ligand slowly ran out from the binding
pocket. *My questions are*: should I apply a small constraining force in
order to keep these small ligands in the binding pocket, if so, then how
to subtract this energy when MM/PBSA is applied to calculate the binding
energy of the complex? Or should I refine my equilibrium and MD protocol to
be gentler so that the ligand might stay in active site for longer time? Or
should I just leave it as it is (not all of them ran out of pockets, just
around half of these small ligands did)?
MD preparation details are listed in below and the input files are attached:
1. small ligands were docked into the active site and two conformations for
each were kept for MD runs.
2. two steps minimization (waters; whole system).
3. heat (Langevin temperature control; restraint_wt=2.0; 50 ps), density
(restraint_wt=2.0; 50 ps) and equilibration (restraint_wt=0.5; 500 ps).
4. production (8 ns)
Thanks,
Tian
Graduate student
College of Pharmacy
University of Illinois at Chicago
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
- application/x-extension-in attachment: heat.in
- application/x-extension-in attachment: equil.in
- application/x-extension-in attachment: prod.in
Received on Sun Feb 19 2012 - 16:00:03 PST
