The Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Samer Gozem from Georgia State University to investigate the molecular and electronic events that occur in Light-Oxygen-Voltage (LOV) protein domains following light excitation. The earth’s surface receives the majority of its energy from solar radiation. Organisms that depend on solar energy, such as algae and plants, must sense and respond to changing light conditions. LOV domains are a class of proteins that use the molecule flavin to absorb light and help organisms sense their environments. Dr. Gozem will apply a combination of classical and quantum mechanical computer simulations to study how specific amino acids in the protein coordinate changes in the electronic structure of the flavin in LOV domains upon light absorption. The fundamental principles to be established by this study have potential long term impact for the design of LOV-based encodable biosensors, light switches, and generators of reactive oxygen species. The project is anticipated to develop automated and user-friendly computational chemistry tools that are more readily accessible to non-computational students and scientists. High school and undergraduate students, including those from under-represented minority groups, are to be introduced to multidisciplinary science and research using these computational tools in research immersion activities. An additional educational goal is to assess the impact of introducing an interdisciplinary course connecting quantum mechanics to chemistry and biology into the curriculum at Georgia State University.
LOV photoreceptors bind the ubiquitous biological cofactor flavin, but undergo distinct photochemistry from other flavoprotein photoreceptors. Upon excitation, the LOV flavin undergoes intersystem crossing to a triplet state, forms an adduct with a nearby conserved cysteine residue, induces an allosteric response, and then reverts to the dark state thermally or, in some cases, photochemically. However, the details of this mechanism vary in different organisms or upon mutagenesis. This project will investigate the mechanistic details of each step of the LOV photocycle in prototypical LOV domains from three kingdoms of life (plants, bacteria, and fungi) and seeks to elucidate how LOV domain protein sequence variations alter the photophysical and photochemical properties of the flavin cofactor. The computational methods being developed and employed in this research include electrostatic tuning maps and hybrid quantum mechanical/molecular mechanical (QM/MM) tools. The QM/MM calculations are being performed with an MM subsystem that partially captures the protein structural ensemble generated by molecular dynamics simulations to sample local side chain flexibility.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
