Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Poster Abstracts

13-POS Board 13 COUPLING FORCES AND HELIX GEOMETRY IN MEMBRANE RECEPTORS: INSIGHTS FROM RIGID-BODY SIMULATIONS OF APO AND LIGAND-BOUND STATES Victor Gabriel Ungureanu 1,2,3 ; Teodor Asvadur Sulea 1 ; Andrei Jose Petrescu 1 ; Laurentiu Spiridon 1 ; 1 Institute of Biochemistry of the Romanian Academy, Bucharest, Romania 2 Genomics Research and Development Institute, Bucharest, Romania 3 Elias University Emergency Hospital, Bucharest, Romania Introduction: Transmembrane helices movements are central to the function of GPCR receptors and underlie the structural adaptation required for ligand accommodation. However, the mechanical forces governing helix mobility within the lipid bilayer—and their relationship to helix geometry—remain insufficiently characterized. Methods: Here, we investigate the determinants of helix displacement of GPR40 receptor (FFAR1), embedded in an explicit lipid environment, using Robosample – a high-speed robot-mechanics based molecular simulation software which combines atomistic with rigid body simulation within a Gibbs sampling framework. Simulations were used to isolate collective motions and to quantify how spatial forces and torques drive the geometric parameters of the helical bundle, including tilt, rotation and interhelical spacing, linking mechanical drivers with structural organization. Results: Simulations are performed for both the ligand-free receptor and ligand-docked complexes, enabling direct comparison between intrinsic conformational dynamics and ligand-induced rearrangements. Comparing apo and ligand-docked simulations reveals how binding redistributes membrane and interhelical forces to reshape the receptor bundle. By analyzing coupled mechanical and geometric descriptors, we pinpoint the pivot regions and displacement pathways that drive structural adaptation and regulate binding site access. Conclusions: This work provides a mechanistic framework connecting forces, helix geometry, and ligand accommodation in membrane proteins. The rigid-body dynamics approach offers an efficient strategy to probe collective motions and complements atomistic simulations in the study of large-scale conformational transitions.

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