Life Sciences Commons^™

Understanding And Exploiting Protein Allostery And Dynamics Using Molecular Simulations, Sukrit Singh

Arts & Sciences Electronic Theses and Dissertations

Protein conformational landscapes contain much of the functionally relevant information that is useful for understanding biological processes at the chemical scale. Understanding and mapping out these conformational landscapescan provide valuable insight into protein behaviors and biological phenomena, and has relevance to the process of therapeutic design.

While structural biology methods have been transformative in studying protein dynamics, they are limited by technicallimitations and have inherent resolution limits. Molecular dynamics (MD) simulations are a powerful tool for exploring conformational landscapes, and provide atomic-scale information that is useful in understanding protein behaviors. With recent advances in generating datasets of large timescale simulations …

Structure And Dynamics Of A Small Multidrug Resistance Transporter, Emre, Chao Wu

Arts & Sciences Electronic Theses and Dissertations

EmrE is a small multidrug resistance transporter in E. coli. It effluxes a wide range of antibiotics, thus contributing to the evolving epidemic of drug resistance. Despite its small size, EmrE is a fully functional transporter making it an ideal model system for a comprehensive study of the multidrug transport mechanism. In the transport cycle, EmrE must alternate between outward- and inward-facing conformations upon substrate binding to translocate substrates across the membrane. High-resolution structures of EmrE in complex with substrates facing different sides of the membrane will shed light on the coupling mechanism between substrate binding and transport. However, the …