Biophysical Society Conference | Tahoe 2023

Proton Reactions: From Basic Science to Biomedical Applications

Tuesday Speaker Abstracts

PROTON-COUPLED ELECTRON TRANSFER IN PROTEINS Sharon Hammes-Schiffer 1 ; 1 Yale University, Department of Chemistry, New Haven, CT, USA

Proton-coupled electron transfer (PCET) reactions play a vital role in a wide range of biological processes. This talk will summarize the main concepts from our PCET theory and will present applications to the enzyme ribonucleotide reductase (RNR), which is essential for DNA synthesis, and the blue-light using flavin (BLUF) photoreceptor protein, which is important for the light regulation of many physiologically important processes. Our general theoretical formulation for PCET includes the quantum mechanicalb effects of the electrons and transferring protons, as well as the motions of the donor-acceptor modes and solvent or protein environment. This PCET theory enables the calculation of rate constants and kinetic isotope effects for comparison to experiment. A combination of computational methods allows atomistic simulations of equilibrium and nonequilibrium PCET processes. The first application discussed will be the enzyme RNR, which requires radical transfer over a PCET pathway composed of six PCET reactions spanning more than 32 Angstroms across an aqueous interface. Our quantum mechanical/molecular mechanical (QM/MM) free energy simulations provide insight into the roles of conformational motions, hydrogen bonding, and proton relays. Our PCET theory elucidates the role of hydrogen tunneling and excited vibronic states. The second application discussed will be the Slr1694 BLUF photoreceptor protein. Photoexcitation to a locally excited state within the flavin instigates electron transfer from a tyrosine to the flavin, followed by proton transfer from this tyrosine to the flavin and then a reverse PCET that produces the light adapted signaling state. Our excited state QM/MM molecular dynamics simulations provide insights into the nonequilibrium dynamics of photoinduced PCET in the BLUF photocycle as well as the nature of the elusive light-adapted state. Overall, our theoretical studies highlight the importance of electronic and nuclear quantum effects, as well as conformational sampling and dynamics, in biological PCET processes.

BIOMOLECUJLAR SIMULATIONS AT CONSTANT PH WITH GPU-ACCELERATED FAST MULTIPOLES ELECTROSTATICS Helmut Grubmüller Max Planck Institute, Germany No Abstract

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