Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Wednesday Speaker Abstracts

DYNAMIC HYDROGEN-BOND NETWORKS FOR G PROTEIN COUPLED RECEPTOR ACTIVATION Eva Bertalan 3 ; Matthew J Rodrigues 4 ; Ching-Ju Tsai 5 ; Gebhard F Schertler 5 ; Ana-Nicoleta Bondar 1,2 ; 1 University of Bucharest, Faculty of Physics, Magurele, Romania 2 University of Bucharest, Faculty of Interdisciplinary Sciences, Bucharest, Romania 3 Physikzentrum, RWTH-Aachen University, Aachen, Germany 4 Diamond Light Source, Harwell Science and Innovation Campus, Didcot, United Kingdom 5 Paul Scherrer Institute, Center for Life Sciences, Villigen, Switzerland G Protein Coupled Receptors use hydrogen(H)-bond networks to couple ligand binding with protein conformational dynamics, activation, and the binding of cytoplasmic interaction partners. These long-distance H-bond networks are typically mediated by water molecules, tend to be dynamic, and can include titratable residues whose protonation changes during receptor function. To study the role of dynamic protein-water hydrogen-bond networks in GPCRs we developed graph-based algorithms and tools. We apply our methodologies to study the assembly and role of internal H-bond networks in a visual receptor of interest as optogenetic tool. From multiple simulations of wild-type and mutant receptors we find that about half of the H-bond network at the ligand-binding site consists of interactions with one conformational mode; the other half of the network consists of interactions that are more dynamic, with two or more conformational modes. H-bonds with more than one conformational mode could help facilitate the propagation of changes in receptor structure and dynamics during activation.

38