[AMBER] Disparities between dG solv from GB and PB Models

From: mish <smncbr.gmail.com>
Date: Sat, 13 Feb 2021 15:55:33 -0600

Dear all,

I am trying to calculate the binding free-energy of hydrophobic molecules
with a protein using MM/GBSA, and MM/PBSA approaches. I did enthalpy
calculations using igb 1, 2, 5, 7, and 8 separately with appropriate VDW
radii sets mentioned in the Amber20 manual. This all looked fine (obtained
binding energies in the range of -50 to -70 kcal/mol) until I did MM/PBSA
calculations on the same system. While doing MM/PBSA, I get +ve binding
free energy, and a difference of about +70 kcal/mol is caused by large
positive dE_SA (ENPLOAR + EDISPER) values in MM/PBSA (~ +40 kcal/mol). I
used radiopt=0, cavity_surften-0.378, cavity_offset=-0.5692 with all four
vdW radii sets (bondi, mbondi, mbondi2, mbondi3) and I am getting exactly
same dE_SA values.

I wonder what could be the source of such a different discrepancy between
MM/GBSA and MM/PBSA entropy values. I am worried that something might be
technically wrong as the MD simulations were run using CHARMM forcefield,
and I am convertingCHARMM topology file into Amber topology using parmed. I
believe it is still using CHARMM forcefield parameters in the calculations
(other than vdW radii sets that I changed using --radii option in the
ante-MMPBSA.py script. Can someone help understand why dE_SA (ENPLOAR +
EDISPER) is positive and different from dE_SA (ESURF) from MM/GBSA?

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Received on Sat Feb 13 2021 - 14:00:02 PST
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