Event

Special Bioengineering Seminar: Troy Cellmer

Wednesday, March 31, 2010
11:00 a.m.
Room 1105 (Pepco Room), Kim Engineering Building
Professor Sameer Shah
sameer@umd.edu

The Ultra-Fast Folding of the Villin Headpiece Subdomain: New Insight from Laser Temperature Jump Measurements and a Simple Analytical Model

Presented by Troy Cellmer
NIH

An understanding of how a protein adopts its three-dimensional structure has captivated scientists working at the interface of biology, chemistry, and physics for several decades. Advances in experimental techniques have facilitated the study of ultra-fast folding proteins (~1-10μs); proteins that fold with a small or nonexistent free-energy barrier. As these proteins are typically small and structurally simple, they provide excellent systems for studying the physics of protein folding and for direct comparisons to state-of-the-art computer simulations. I will present experimental and theoretical results pertaining to the ultra-fast folding villin headpiece subdomain, one of the most widely studied molecules in biophysics. To begin, I present thermodynamic and kinetic data for villin folding in denaturant concentration. Unlike any other study, we find that the relaxation rate is independent of chemical denaturant. Results from these experiments are analyzed using an Ising-like model for protein folding, and the connection between free-energy barriers and chevron plots is discussed. Next, I present experimental data pertaining to the viscosity-dependence of villin’s folding kinetics. I show how these results can be used to calculate the protein’s internal viscosity. Analysis with the Ising-like model yields novel insight into the origins of internal friction in protein folding. To conclude, I discuss ongoing work aimed at further challenging our theoretical model by measuring the effects of mutations on villin’s folding behavior.

Audience: Graduate  Faculty  Post-Docs