Biophysical Society Conference | Tahoe 2023

Proton Reactions: From Basic Science to Biomedical Applications

Monday Speaker Abstracts

MEMBRANE PROTEIN THERMODYNAMIC MEASUREMENTS ENABLED BY PROTONS Karen Fleming John Hopkins University, USA No Abstract DYNAMIC HYDROGEN-BOND NETWORKS FOR PROTON BINDING AND PROTON TRANSFER AT BIO-MEMBRANE INTERFACES Eva Bertalan 1 ; Honey Jain 2,3 ; Joseph Matthew Rodrigues 4 ; Gebhard F Schertler 4 ; Leonid Brown 5 ; Ana-Nicoleta Bondar 2,6 ; 1 Physikzentrum, RWTH-Aachen University, Aachen, Germany 2 University of Bucharest, Faculty of Physics, Bucharest-Magurele, Romania 3 Freie Universität Berlin, Physics Department, Berlin, Germany 4 Paul Scherer Institut, Laboratory of Biomolecular Research, Villigen, Switzerland 5 University of Guelph, Department of Physics, Guelph, ON, Canada 6 Forschungszentrum Jülich, Institute for Computational Biomedicine (IAS-5/INM-9), Jülich, Germany Membrane proteins that bind and transfer protons to and from the bulk often rely on water mediated hydrogen-bond networks that contain titratable sidechains and couple to other functionally important sites of the protein. As such networks may extend throughout a significant region of the protein, the identity of the proton-binding sites and the response of the protein to protonation change can be difficult to predict. We develop and apply graph-based algorithms to compute and dissect hydrogen-bond networks in proton-binding membrane proteins and at the interfaces of lipid membranes with different lipid composition. From analyses of datasets of membrane protein structures from structural biology and simulations, we identify structural and sequence motifs of proton-binding hydrogen-bond networks. Depending on the identity of their headgroups, lipids can directly participate in dynamic hydrogen-bond networks with titratable sidechains at proton uptake/release sites of proton-coupled membrane transporters. Research was supported in part by the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie grant agreement No 860592, Innovative Training Network ‘Proton and proton-coupled transport’, and by computing time from the Physics Department of the Freie Universität Berlin and from the Forschungszentrum Jülich. DECIPHERING APPARENT CHOLESTEROL EFFECTS ON VOLTAGE-GATED PROTON CHANNELS

Thomas DeCoursey Rush University, USA No Abstract

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