Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Poster Abstracts

12-POS Board 12 INCREASED ACCURACY OF GPCR MOLECULAR DOCKING SIMULATIONS BY INCLUSION OF MEMBRANE-INDUCED DESOLVATION CONTRIBUTIONS Teodor A Sulea 1 ; Cosmin Trif 2 ; Sorin Tunaru 2 ; Laurentiu Spiridon 1 ; Andrei J Petrescu 1 ; 1 Institute of Biochemistry of the Romanian Academy, Department of Bioinformatics & Structural Biochemistry, Bucharest, Romania 2 Institute of Biochemistry of the Romanian Academy, Cell Signaling Research Group, Bucharest, Romania G-protein Coupled Receptors are a family of transmembrane proteins ubiquitously found across all types of human tissue being one of the main pharmacological target with about a third of the overall approved drugs, and a potent target for de novo drug development or drug repurposing studies. When assessing the binding ability of a large library of putative interactors, Virtual High-Throughput Screening (V-HTS) is used, which classifies the library into binders and non binders through molecular docking simulations. Thus, in order to minimize the risk of false negatives, an accurate docking protocol is necessary. In the current work, we present a novel docking protocol which significantly improves contact profiles for transmembrane receptors. While the effect of explicit membrane in MD has been studied [1], its inclusion in molecular docking has not been as thoroughly discussed. The inclusion of explicit membrane lipids during docking will be a steric deterrent and any sites inside the bilayer will not be explored. However, not representing the bilayer at all will lead to the environment of the protein being treated as pure solvent, leading to hydrophobic ligands being scored worse and as such be reported as false negatives in V-HTS studies. Through successive explicit equilibration rounds and intelligent generation of desolvation contribution grids, we can mimic the hydrophobic contribution of the membrane without imposing steric restrictions on the pose generation process. Using this method we have generated more accurate poses for a set of crystallized ligands. Acknowledgement: This research was supported by The Ministry of Investments and European Projects, through the Managing Authority for the Health Program, PS/272/PS_P5/OP1/RSO1.1/PS_P5_RSO1.1_A9– ROGEN Project (MySMIS 324809) and The Romanian Academy [1] Sengupta D et al. Exploring GPCR–Lipid Interactions by Molecular Dynamics Simulations: Excitements, Challenges, and the Way Forward. The Journal of Physical Chemistry B 2018; 22 (22), 5727 5737. doi: 10.1021/acs.jpcb.8b01657.

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