Quantum Dynamic Investigations of Redox in Biology

Cornell University, Ithaca NY

Investigators

Abstract

Project Summary Establishing a fundamental understanding of redox processes in biology is a key challenge with the potential to transform research in areas ranging from the development of biomimetic materials for efficient energy harvesting, small molecule drug design to mitigate disease pathways, and even in the search for quantum materials that exhibit sensitive control of electrons and spin dynamics. While electronic structure theory and multiscale methods like QM/MM can uncover experimentally inaccessible intermediate structures and even provide insights into some thermodynamic properties these methods are inherently static and do not account for quantized nuclear motion. Using the path integral formulation of quantum mechanics, we will build a theoretical framework that retains the computational efficiency of classical molecular dynamics but that can elucidate kinetic factors – uncover reaction pathways and compute rates – while taking into account the inherently quantum nature of charge transfer by capturing zero-point energy, tunneling, and even quantum coherence effects. Working with experimental collaborators, we will build a broadly applicable simulation toolbox for the characterization of redox processes in biology and we will demonstrate them on model systems including a nitrification enzyme, a multi-metal center drug candidate, and a radical relay protein that exhibits long range electron transfer (ET). These studies will allow us to answer key outstanding questions in redox biology: (i) Can we ‘see’ the sequence of electrons and protons transfer events in enzyme active sites? What residues control the order and efficiency of the transfer events? (ii) How does the environment (solvent, co-localized small molecules, metal centers, crowding) affect redox reactivity? Can we identify pathways for decoherence and energy dissipation and corresponding control strategies? (iii) What are the key dynamically and statistically correlated fluctuations that drive long range ET? Can we identify fundamental design principles for efficient long range ET?