Prof. Dilip Asthagiri, Johns Hopkins University
April 25, 2013
12:00 AM - 12:00 AM
Thermodynamics of Protein Folding and Stability: a Quasichemical Perspective
Abstract:
The stability of a folded protein against unfolding is usually small, being only about a few times the typical strength of a hydrogen bond in water. This modest stability arises from a balance of large competing hydration effects and intra-molecular interactions in the protein. Nature provides examples of both cases where this balance is specifically altered, as happens in the metal-induced folding of an otherwise unstructured peptide, and where the balance is preserved by changing solvent conditions using osmolytes, as happens in the face of extremes of temperature or pressure or presence of solutes that can denature the protein. Elucidating the physics underlying such protein-solvent adaptation is a fundamental challenge in biology and the principal focus of our research efforts. In seeking a molecular scale understanding of the thermodynamics of the protein in the solvent milieu, we deal with a many-body system characterized by many different scales of length and of interaction energies. Acknowledging these challenges, we have developed a theoretical and computational framework that allows, for the first time, a clear examination of the excess free energy of the protein in a given solvent. I will present the main ideas behind this framework and illustrate it with examples on the hydration of the Ca(2+) ion and the protein cytochrome C. Then I will consider in detail the role of trimethylamine-n-oxide, an osmolyte, and urea in the coil to helix transition of a deca-alanine peptide. As part of our research on thermodynamics of protein folding, we are also studying metal-induced folding of unfolded peptides. Time permitting, I will present our studies on metal selectivity in a zinc finger protein, a system where metal binding and folding are coupled.
Date posted
Jun 17, 2019
Date updated
Jun 17, 2019