Application of molecular modeling techniques to study the structure, dynamics, and interactions of membrane proteins.

Abstract

Membrane proteins constitute ~30% of all the genomes and ~70% of the drug targets. However, less than 1% of the entries in the protein data bank are membrane proteins. The underrepresentation of membrane protein structures limits our understanding of their functions. This thesis summarizes my effects to apply theoretical methods to understand the structure and function relationships of membrane proteins. Specifically, we developed computational techniques to interpret solution and solid-state NMR data of membrane proteins and determine their high resolution structures. We further performed molecular dynamics simulations to study their dynamics, interaction with other proteins and the lipid bilayer environment. We applied these approaches to phospholamban, which is a membrane protein that is involved in cardiac muscle relaxation by regulating Ca2+-ATPase activity. Our results provide new insights to understand how membrane proteins elicit their function.