Physics Colloquium, October 31, 2006

The Fundamental Processes of Protein Folding

R. Brian Dyer

Los Alamos National Lab

Understanding how a protein folds to its native, biologically active structure is a central problem of modern biology, with important practical consequences for rational protein design, protein structure prediction and folding related disease states. The specific function of a protein is determined by its structure and the ability of the structure to evolve with time. The three dimensional structure, in turn, is completely determined by the sequence of amino acids of its polypeptide chain, at least for small proteins and probably for all proteins in a general sense. Moreover, the amino acid sequence codes the folding dynamics, shaping the energy landscape such that the folding process quickly finds the global minimum (the native structure) in the vast conformational space available to the polypeptide chain. Recent experimental and theoretical studies suggest that the most fundamental processes in protein folding occur on time scales from 10^-9 to 10^-3 s, including secondary structure formation, hydrophobic collapse and sidechain packing. Are there characteristic rates for these processes, and if so, what are they, how are they coupled and how do these rates influence or control the overall folding process? We have used laser induced temperature-jump relaxation techniques and time-resolved infrared and fluorescence spectroscopies to probe these dynamics in peptide models, and small, single domain proteins.

4:00 p.m., Physics Research Building (PRB), Room 1080

Reception at 3:45 p.m., Atrium, PRB