Dalia Rokhsana of Whitman College is supported by an award from the Chemistry of Life Processes Program in the Division of Chemistry to investigate the reactivity of molybdenum-based enzymes, bacterial proteins that catalyze water-splitting reactions to produce hydrogen gas. Hydrogen is an important "green" energy source for fuel cells, propulsion systems, and combustion engines. Rokhsana and her group are using state-of-the-art computational chemistry and molecular modeling techniques to understand how the protein active site controls structure, function, specificity, and reactivity. This research has potential applications to the biomimetic design and optimization of large-scale hydrogen gas production. The project is supporting undergraduate student engagement at this primarily undergraduate institution. These students co-author scientific papers, and make presentations at national meetings and regional conferences. External collaborations with leading computational scientists enhance the integration of scientific discovery with student education, in keeping with the teacher-scholar model promoted at Whitman College. Problems based on the research are integrated with coursework in computational chemistry and biochemistry.
One chemical functions of biological systems is the activation of inert small molecules under ambient conditions. Understanding the molecular mechanism of these processes is a challenging areas at the interface of biology and chemistry. In this project, Rokhsana and her group are focusing on a diverse family of molybdenum enzymes that catalyze oxo-transfer to interconvert various substrates (carbon monoxide, sulfite, arsenite, etc.) into products, while splitting water into protons and electrons. This research focuses on a poorly-understood bimetallic [Mo-S-Cu] active site of a Mo-enzyme, CO dehydrogenase. The first aim is to investigate the composition of the active site as a function of redox-, spin-, and protonation-states. The second aim is to characterize geometric and electronic structures of intermediates and transition states during the non-reversible, catalytic transformation of carbon monoxide into carbon dioxide. A computational approach is necessary due to the lack of direct and unambiguous information about intermediates from experiments. Rokhsana and her group are utilizing realistic quantum mechanical (QM) and extended quantum mechanical/molecular mechanical (QM/MM) models to systematically and comprehensively investigate the effect of protein environment on the geometric and electronic structure of the active site, and understand how the inner coordination sphere and outer protein environment control and tune metalloenzyme function. This work may providing insights into the overall catalytic mechanism of CO oxidation, with application to molecular engineering of biomimetic systems for the water splitting reaction. The project is immersing undergraduate students in comprehensive and complementary bioinorganic and computational chemistry research involving state-of-the-art modeling and simulation techniques. The new course is helping meet the considerable demand for research opportunities requested by students at Whitman College, and facilitating new collaborations and engagement with the broader chemistry community.
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.
