SOLID STATE NMR STUDIES OF PEPTIDES AND PROTEINS

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (Adapted from abstract): This proposal focuses on the development of solid state NMR methods for the characterization of 3D structures of proteins and peptides and the accomplishment of those structures. Peptide and protein structure will be demonstrated first with the short peptide MLF and then with protein G. The primary approach will be to use torsional constraints in crystalline samples for the local structure and distances for the long-range constraints. The research will employ innovative isotopic labeling schemes. Complex structures will be characterized with erythromycin/ribosome complex, the ribonucleotide reductase inhibitor complex and characterization of the potential low barrier hydrogen bond in lytic protease. The project with bound EA will dramatically push the limits of solid state NMR sensitivity. Negative labeling with 2H and 12C as well as the potential of using DNP (dynamic nuclear polarization) are presented. Protein dynamics will be characterized focusing on MLF and protein G, a complete characterization of dynamics in these systems is sought with 15N and 2H lineshapes and 2H relaxation. Method development will occur throughout this project to achieve the necessary goals of sensitivity, selectivity, assignments, and structural constraints.