Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Poster Abstracts

40-POS Board 20 IN-SILICO VALIDATION OF BINDING AFFINITIES FOR BIOLOGICAL GPCRS WITH BAR ALGORITHM Sangbae Lee ; Minkyu Kim 1 ; Jian Jeong 1 ; Donghwan Kim 1 ; Sangbae Lee 1 ; Art E Cho 1 ; 1 inCerebro, Seoul, South Korea Binding affinity prediction of ligand-receptor complex structure using computational approach often falls short in providing satisfactory validation of experimental results due to frequent insufficient sampling. As a solution to these challenges, re-cent emphasis has been placed on the re-sampling of new trajectories, and in this study, we propose a simulation protocol that achieves efficient sampling. We have re-engineered the widely used Bennett acceptance ratio (BAR) method as a representative approach and tested its efficacy across various membrane protein targets to verify its efficient applicability to the targets. We chose GPCR (G-protein coupled receptor) targets with diverse structural landscapes and experimentally validated binding affinities. Subsequently, using BAR-based binding free energy, we confirmed correlations to demonstrate the validity and performance of the computational approach.

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