Unraveling Connections Among Biomolecular Structure, Interfacial Solvent Dynamics, and Conformational Dynamics

Wichita State University, Wichita KS

Investigators

Abstract

The Chemical Structure, Dynamics, and Mechanism B Program (CSDMB) of the Chemistry Division supports the project by Professors Katie Mitchell-Koch and Vinh Nguyen. Professor Mitchell-Koch is a faculty member in the Department of Chemistry at Wichita State University, and Professor Nguyen is a faculty member in the Department of Physics at Virginia Tech. Their research focuses on the dynamics or movement of solvent molecules around enzymes. Enzymes are molecules that effect chemical reactions in living systems. They do so with remarkable efficiency and selectivity. Their ability to perform these tasks depends on their ability to be flexible. This flexibility is strongly influenced by interactions between the surface of the enzyme and the solvent it is dissolved in, and in particular how well different parts of the enzyme can "slip through" that solvent. Because of the importance of these interactions, the design of new artificial enzymes relies on understanding how enzymes influence the movement of solvent molecules on their surface and in turn how those features influence how the enzyme moves and behaves. With this in mind, Professor Nguyen is developing unique methods that allow his group to gather data on both solvent movement and movement within the enzyme at the same time. To compliment these efforts, Professor Mitchell-Koch employs computational chemistry techniques to provide insights into how specific features of the enzymes surface change the way the surrounding solvent behaves and ultimately improve performance of the enzyme. In this way, the work is poised to guide protein engineering and design of new biocatalysts for greener production (lower energy costs, higher atom efficiency) of fine chemicals and pharmaceuticals. The research provides valuable opportunities and resources for interdisciplinary training and mentoring of undergraduate and graduate students. Professors Mitchell-Koch and Nguyen have a strong track record of training undergraduate and graduate students including those from underrepresented groups in STEM, and they will continue to recruit and train students to contribute to our nation's capacity for science and technology. Their outreach activities with middle school and high school students as a part of the project will strengthen the impacts of the research. Solvent-compatible enzymes (those that function in organic solvents) present an ideal platform for studying connections between interfacial solvent dynamics and molecular structure, dynamics, and mechanism, since enzymatic activity is influenced by protein conformational dynamics. The project employs the world's highest precision, highest sensitivity and largest continuous-frequency gigahertz to terahertz spectrometer (with power signal-to-noise up to 1015 and spectral resolution less than 100 Hz), combined with molecular dynamics simulations to map protein solvation and molecular interactions around the surface of biomolecules. Solvents with differing chemical properties serve as variables, altering intermolecular interactions with the surface that in turn modify solvent dynamics. Literature reports support a connection between interfacial solvent dynamics and protein dynamics in both aqueous solutions and organic solvents. In this effort, the PIs hypothesize that there is a feedback loop between structure-modified solvent dynamics and solvent dynamics-protein dynamics that may serve as a protein design principle. A distinction in the work is that it focuses on local (region-specific) solvation environments (mapped around the entire protein) rather than analyzing solvation layer properties as a whole (or relying on bulk solvent characteristics), as it is thought that these local effects are the primary arbitrators of solvent dynamics-biomolecular structure-dynamics connections. The project undertakes the first comprehensive study of organic solvent dynamics at the enzyme interface, and their relationship to enzyme structure-dynamics-activity, tying results to measured collective motions and published kinetics values. Since solvation processes are also critical in charge transfer (electron and proton transfer), substrate transport, and molecular recognition, it is imperative to characterize relationships between organic and aqueous solvent dynamics and surface-solvent interactions to inform design of many interfaces, from functional materials to de novo proteins. Interdisciplinary training for undergraduate and graduate researchers with diverse backgrounds is provided in the Mitchell-Koch and Nguyen laboratories. Outreach activities provide awareness of terahertz research, dynamics of biomolecules, and computational chemistry methods to the public and community groups. The Summer NanoCamp at Virginia Tech gives students, including those in under-represented groups, their parents/guardians, and school teachers, the ability to participate in activities designed to foster engagement and interest in nanoscience, including gigahertz to terahertz science. A workshop on Brownian motion will provide experimental observations and videos of simulations data, reaching middle school girls at annual Expanding Your Horizons events at Wichita State. This program will also be available in K-12 outreach presentations. Assessment of broader impacts includes longitudinal tracking of research students and teacher/student/parent surveys for outreach activities.