[AMBER] MMPBSA.py and rms fit: Results depend on reference frame

From: Lennart Gundelach <L.Gundelach.soton.ac.uk>
Date: Wed, 12 May 2021 07:33:55 +0000


To run MMPBSA with explicit waters I have been feeding single snapshots to the MMPBSA.py script because each snapshot has a different number of waters, so I canít generate a sensible trajectory/topology file. To validate my snapshot-wise approach, I calculated binding energies of the protein-ligand complex WITHOUT explicit waters using both the usual trajectory file and a snapshot by snapshot approach. I could however not reproduce the energies. This was because the MMPBSA.py script does an autoimage and rms fit on the whole trajectory before calculation energies or entropies (which it obviously cant in the snapshot by snapshot approach).

I have naively been assuming, that the energies obtained would be invariant under rotations and translations of the system and that the final energies would not depend on the choice or reference frame or ordering of the trajectory. This is not the case.

Is this to be expected or intended, or does it indicate an underlying problem with my topology/coordinates?

My fix is simply to autoimage and rms fit the trajectory before slicing it into individual snapshots, but I still wonder if there is something else going wrong, leading the this dependence of the energies on the details of the rms fit of the trajectory. To be honest I donít understand why the rms fit is performed in the first place.

Thanks you and best wishes,

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Received on Wed May 12 2021 - 01:00:02 PDT
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