Molecular modeling of charge transfer in heme-containing systems: a time-dependent view

• Applicant: Professor Dr. Ulrich Kleinekathöfer
• Subject Area: Biophysics ; Theoretical Chemistry: Electronic Structure, Dynamics, Simulation
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533004272

Hemeproteins represent a large class of metalloproteins, where the heme groups confers functionality, including oxygen-carrying, oxygen reduction, electron transfer, and other processes. At the same time, these proteins are among the most studied biomolecules because of their diverse biological functions and widespread abundance. Some systems contain a small number of heme groups, potentially among other redox centres, while other proteins include many heme groups to facilitate charge transfer over relatively large distances. The electron transfer in heme-containing proteins has been proposed to follow various mechanisms from sequential hopping over flickering resonances to purely coherent transfer. This project aims at providing a general recipe for how to treat electron transfer in heme-containing proteins with no prior assumptions on the specific mode of electron transfer, i.e., without any prejudice. To justify the generality of the to-be-developed protocols, we will study electron transfer processes in a molecular system with a few heme-groups and relatively short electron transfer processes, i.e., the cytochrome bc1 complex, and a protein complex that can potentially polymerize and lead to long-range electron transfers, i.e., the OmcS protein. Due to the size of the systems, a fully quantum mechanical (QM) description of the processes is numerically prohibitive. At the same time, purely classical molecular dynamics (MD) simulations and ground-state quantum mechanics/molecular mechanics (QM/MM) descriptions are not sufficient due to the inherent limitations of these representations. Thus, a mixed quantum-classical scheme is in order to delineate the electron transfer process that we aim to exploit for biological systems with clearly defined redox centres between which the transfer takes place. Specifically, we will employ a hybrid procedure using a QM/MM MD approach for the atomic-level dynamics of the electron transfer entities combined with a coarse-grained quantum dynamical description of the actual electron transfer extending an earlier scheme using MD instead of the now proposed QM/MD simulations for the molecular-level description. To carry out the full-scale electron transfer simulations in heme-containing proteins, fundamental advances have to be made in methods in computational biophysics. A comprehensive framework for quantum-classical electron transfer simulations will be the first outcome of this project. The second outcome will include complete simulations of the bc1 complex and the OmcS system that will ultimately allow us to answer fundamental questions in biophysics such as: How does the function of partial processes in the bc1 complex at the quantum level facilitate integration into the overall mechanism for energy conversion? Which effects do fluctuations and coherences have on the electron transfer through an OmcS nanowire?

• DFG Programme: Research Grants