Ionizable Residue Interactions in Tilted Transmembrane Helices

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This project addresses fundamental gaps in understanding the consequences of ionization and dynamics for the biological function of proteins in lipid-bilayer membranes. Solid-state magnetic resonance experiments will provide crucial benchmarks for the validation and integration of theory, computation and experiment. The experiments will employ a novel ?host? peptide design, in which minimal numbers of chemically distinct aromatic amino acid residues serve to position a tilted transmembrane helix near a ?tipping point? in lipid bilayer membranes. Within this context, the systematic incorporation of specific ionizable (potentially charged) ?guest? residues will provide important new insights concerning ionization behavior and protein-lipid molecular interactions that are essential for the biological functions of many classes of membrane proteins. In addition to fundamental insights about lipids and proteins, the project will advance the understanding of molecular mechanisms that may govern the functioning of potassium channels, acetylcholine receptors and integrins, among other membrane proteins. The project will extend longstanding commitments to community outreach and early involvement of undergraduate students in cutting-edge research. An overarching goal is the recruitment of new creative minds to lifelong careers dedicated to scientific discovery, while at the same time broadening the base for participation of non-traditional individuals and underrepresented groups in science. The project will contribute and enhance the undergraduate research opportunities?beginning at the freshman and sophomore levels. Additional efforts are devoted to the coordination of a statewide infrastructure for undergraduate research in Arkansas, a community Science Café and a protein virtual reality lab.