Dear Amber Users,
I am currently working on a protein anchored in a membrane bilayer. After equilibrating the system for 100 ns, I docked the potential ligand using AutoDock Vina and ran another 100 ns of simulations. The ligand consistently occupied the binding site. Subsequently, I performed MM-GBSA calculations and obtained a small but positive value for the interaction energy:
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Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of Mean
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VDWAALS -11.9224 2.2582 0.0226
EEL -60.8192 15.3864 0.1539
EGB 75.4142 12.6881 0.1269
ESURF -2.6166 0.1865 0.0019
DELTA G gas -72.7415 14.6457 0.1465
DELTA G solv 72.7976 12.6124 0.1261
DELTA TOTAL 0.0561 3.1697 0.0317
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For your reference, the input used is as follows:
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&general
strip_mask = :WAT:K+:Cl-:PA:PE:OL:PC",
/
&gb
saltcon=0.150,
/
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I generated topologies using the command:
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ante-MMPBSA.py -p MD.prmtop -c COMPLEX.prmtop -r RECEPTOR.prmtop -l LIGAND.prmtop -s :WAT:K+:Cl-:PA:PE:OL:PC -n :FST
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Given the small positive interaction energy, I am wondering what could be the reason for this result. How should I interpret this value in the context of the expected binding affinity toward the pocket where the ligand was docked? Would doing MM-PBSA be a „solution” for the issue?
Thank you for your insights.
–
Maciej Spiegel, MPharm PhD
assistant professor
.GitHub <
https://farmaceut.github.io/>
Department of Organic Chemistry and Pharmaceutical Technology,
Faculty of Pharmacy, Wroclaw Medical University
Borowska 211A, 50-556 Wroclaw, Poland
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Received on Sun Sep 08 2024 - 10:30:02 PDT
