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.
