Investigation of Long-Range Charge Transfer and Excited State Processes in Biochemical Systems

PROJECT SUMMARY/ABSTRACT In this MIRA program, we aim to gain atomic-level insights into complex biological systems such as bacterial membrane proteins and light-sensitive proteins with particular emphasis on their native protein and lipid environments. We will test the impact of such biochemical environments in two distinct projects.

A wide variety of toxic chemicals, including toxic metal oxides and hydroxides, pollute our environment, posing an imminent threat to human life. One can leverage the unique respiration mechanism in marine microbes like Shewanella to revolutionize bioremediation and wastewater treatment technology. Molecular modeling and

computations will provide an atomic-scale comprehension of the mechanism that will augment macroscale experimental observables. In the first project, we will model the outer membrane cytochrome-porin complex of Shewanella oneidensis in its native environment and obtain molecular insights into the charge-transfer network employed in

its respiration. Electronically excited-state processes are ubiquitous in nature and biotechnology. For example, blue-light-sensitive proteins are used in the optogenetic control of cellular processes. Fluorescent proteins with emissions spanning the entire visible region are often utilized for in vivo imaging. In these applications, subtle structural changes in an

electronically excited molecule induce pronounced conformational changes in the nearby protein environment or further from its location (allostery). Therefore, the biochemical environment relays the information at the photon-absorption site to another site. Most conformational changes occur well beyond a few nanoseconds, making them

inaccessible to modern multi-scale quantum mechanics/molecular mechanics (QM/MM) techniques. Therefore, in the second project, we will build a tool to model excited states of biomolecules using force field parameters and then validate those parameters using a few case studies with fluorescent proteins. Furthermore, we will use those parameters to

decipher photoinduced allosteric pathways in blue-light-sensitive proteins.