PECASE: Probing protein surfaces using multiple solvent crystal structures

North Carolina State University, Raleigh NC

Investigators

Abstract

Proposal Title: PECASE: Probing protein surfaces using multiple solvent crystal structures Institution: North Carolina State University The objective of the research supported by this PECASE award is to investigate the character of ligand binding sites on proteins using the novel multiple solvent crystal structures method. The idea is to solve the crystal structures of different proteins in a variety of organic solvents in order to map their binding surfaces. The study will focus on five representative proteins that interact with different types of ligands. The premise is that the solvent molecules have characteristics in common with component parts of larger ligands and bind primarily in areas that evolved as binding sites. At the same time, changes in the properties of the bulk solvent relative to an aqueous solution provide changes to the protein environment. Analysis of the protein crystal structures in these multiple environments can be used to delineate structural components that are able to adjust to the change. Are there common patterns of hydration, plasticity and hydrophobic exposed surfaces that are independent of vast differences in shape, dynamics, electrostatic and hydrophobic content of the binding sites? To what extent does the type of ligand determine the surface properties of proteins, and how do dynamics affect the binding site features? Answers to these questions are critical to our basic understanding of protein-protein and protein-ligand interactions and will ultimately help to bridge the gap between what we observe experimentally and what we can predict from first principles. Broader impact: Model building and refinement of the crystal structures will be integrated into an undergraduate course on protein structure and function and into a graduate course on macromolecular modeling. The students taking these courses will work closely with the research team to complete the refinement of the structures. Thus, the scientific objectives of this project will be accomplished within an educational framework designed to enhance the knowledge and research experience of individuals from several stages of the academic ladder. This project aims to 1) decrease the gap between teaching and research experiences of the students, 2) expose a large number of students to the questions guiding cutting edge research while offering students an illustration of the concepts discussed in class, 3) spark an interest in undergraduates, particularly women and Latino students, that might never have had the motivation to inquire about research outside of the classroom and 4) develop a process by which post-docs and graduate students are motivated to be excellent teachers. This project was originally funded as a CAREER award, and was converted to a Presidential Early Career Award for Engineers and Scientists (PECASE) award in September 2004.