Following a 100 ns MD trajectory of a homodimer (trajectory 1), I’ve calculated the free energy of binding of two monomeric subunits of a protein using MMPBSA.py (single trajectory approach) (deltaG = 30 kcal/mol).
I run a second 100 ns MD simulation the same homodimer in complex with identical ligands in each subunit (trajectory 2). I calculated the free energy of binding of the two subunits in the presence of ligands. Subsequently, I used ante-mmpbsa.py to strip the ligands and generate new topologies. The calculated free energy of binding of the two subunits is considerably different from that calculated from trajectory 1 (deltaG = 40 kcal/mol).
It can be argued that this difference is due to the trajectories sampling different conformational spaces. However, I’m wondering if the process of stripping the ligands using ante-mmpbsa.py perturbs the trajectory thus giving a miscalculation of free energies.
Any suggestions would be extremely useful.
Thanks in advance
George
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Thu May 26 2016 - 12:00:03 PDT
