[AMBER] Interpreting energy decomposition in Amber thermodynamic integration

From: Stefan Ivanov <stefan.ivanov.postgrad.manchester.ac.uk>
Date: Fri, 20 Jan 2017 15:28:00 +0000

Dear Amber users and developers,

I would like to ask a few questions relating to the energy decomposition in TI with Amber. I'm not sure how to interpret the results I get. I can't find a paper explaining the principle that per-residue/sidechain/backbone decomposition is based on, so first of all I would like to ask "What is that principle?" Are vdw and electrostatic interactions evaluated for each atom individually and then these values are summed for individual residues to get the vdw and electrostatic energy contributions per residue or does it work in some other way? If so, what is that way? Is the principle the same as used in MMPBSA.py for per-residue decomposition?

I am performing TI, transforming one strong protein binder to another. All protein internal energies are 0, whereas the internal energy for the template ligand and modeled ligand is strongly negative. Why are internal energies non-zero only for the ligands?

In the .out files, are energy values relative or absolute? I.e., if the vdw value for a given residue at = 0.9 is negative and positive at = 0.1, are those values absolute or relative? Are they in kJ/mol or kcal/mol?

How are energy contributions split between the two interacting partners? I have two large hydrophobic ligands bound to a large hydrophobic groove but only 2-3 residues show van der Waals energies different from 0. It appears that most of the residues making hydrophobic contacts with the ligands have had their contributions assigned to the ligands. This relates to my question how decomposition is performed. Is there any way I could perform per-atom decomposition, which would give me much greater resolution?

Finally, I see that there are residues not in any contact with the ligands but 20 angstrom or more away from them that show a considerable energetic contribution, some positive, others negative. This, I imagine, is related to favourable/unfavourable desolvation energies, correct? How are those estimated?

I would be immensely grateful if someone could clarify all this for me.

Sincerely,

Stefan Ivanov

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Received on Fri Jan 20 2017 - 07:30:03 PST
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