Dr. Cecilia Clementi
Department of Chemistry
Rice University
Houston, TX

Monday, April 11, 2005
3:00 pm (CT)
3269 Beckman Institute

Abstract

The detailed characterization of the overall free energy landscape associated with the folding process of a protein is the ultimate goal in protein folding studies. Modern experimental techniques provide accurate thermodynamic and kinetic measurements on restricted regions of a protein landscape. Although simplified protein models can access larger regions of the landscape, they are oftentimes built on assumptions and approximations that affect the accuracy of the results. We present a new methodology that allows to combine the complementary strengths of theory and experiment for a more complete characterization of a protein folding landscape. We prove that this new procedure allows a simplified protein model to reproduce remarkably well (correlation coefficient > 0.9) all experimental data available on free energy differences upon single mutations for S6 ribosomal protein and two circular permutants. In addition, we have recently proposed a novel coarse-grained protein model and a design strategy that circumvent the long outstanding problem of defining effective parameters for a simplified (but not trivial) off-lattice protein Hamiltonian. We show that it is possible to address a minimalist protein representation with a pairwise model Hamiltonian able to fold smoothly into the native state of a selected protein.

Tea and coffee will be served in R3151 Beckman Institute at 2:30pm.