Quantum Effects on Proton Transfer in Biomolecular Environments
Final Report Abstract
Proton transfer belongs to the most fundamental chemical reactions not only in core chemistry but also in biomolecular environments. In particular, vectorial proton transduction in proteins plays a crucial role in photosynthesis, enzymatic reactions, or in pH regulation of the cell. However, the small mass of the proton allows for quantum effects, such as zero point motion and tunnelling, which are well documented by large measured isotope effects. Experiments together with simulations indicate since long that such effects have a major impact on the kinetics of bacteriorhodopsin being a photon–driven proton pump transporting protons through cell membranes to the extracellular medium. Simulation methods that are able to tackle such complex biomolecular processes must include nuclear quantum effects at the first place while treating the electronic structure currently in order to allow for chemical or enzymatic reactions to occur. Secondly, these methods must provice practical access to multi-dimensional free energy landscapes which include not only thermal activation, but also quantum effects on nuclear motion in chemically complex environments. Within this project, the path integral formulation of quantum mechanics has been combined with mixed quantum/classical treatments of the interactions (also known as QM/MM methods), which enables realistic investigations of biomolecular processes which rigorously include nuclear quantum effects such as proton tunneling. Secondly, path integrals have be used to generalize ab initio metadynamics sampling, being a well-established acceleration method, to involve quantum nuclei. The resulting ab initio path integral metadynamics technique allows one to map multi-dimensional quantum free energy landscapes involving high barriers such as those that govern biochemical reactions, e.g. proton or hydride transfer in enzymes, where nuclear quantum effects are rigorously taken into account.
Publications
- Quantum free energy landscapes from ab initio path integral metadynamics: Double proton transfer in the formic acid dimer is concerted but not correlated, J. Chem. Phys. 143, 124304–1-9 (2015)
S. D. Ivanov, I. M. Grant, and D. Marx
(See online at https://doi.org/10.1063/1.4931052) - Free-Energy Landscape and Proton Transfer Pathways in Oxidative Deamination by Methylamine Dehydrogenase, ChemPhysChem 18, 208–222 (2017)
T. Zelleke and D. Marx
(See online at https://doi.org/10.1002/cphc.201601113)
