[AMBER] ante-mmpbsa.py: general question

From: George Tzotzos <gtzotzos.me.com>
Date: Thu, 26 May 2016 21:33:44 +0300

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


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Received on Thu May 26 2016 - 12:00:03 PDT
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