TCBG Seminar

Exploring Free Energy Landscapes in Protein Folding

Professor Charles L. Brooks, III
Department of Molecular Biology
The Scripps Research Institute
La Jolla, California

Monday, March 31, 1997
3:00 pm (CT)
3269 Beckman Institute


The mechanism by which protein molecules fold may be categorized based upon fundamental properties of the folding landscape. Fast folding proteins are predicted to have a smooth landscape and fold under near thermodynamic control. Proteins which fold on a rugged landscape may become trapped in local meta-stable conformations, producing observable folding intermediates. Their progress into the native manifold is determined by the nature of specific interactions. Despite the development of theoretical models for protein folding mechanism that connect properties of the folding landscape to the folding mechanism, our understanding of how the topology of the folded protein and the nature of the protein sequence influence the free energy landscape for folding is still in an early stage. To address these questions, we have used detailed, all atom, and reduced representation models of proteins. We began an exploration of relationships between a protein's fold, sequence and its folding mechanism. First principles calculations of the folding free energy surfaces for all helical, all beta and mixed alpha/beta proteins will be presented that suggest a link between the topology and nature of tertiary interactions made by a native folded protein and the free energy landscape on which folding takes place. These studies provide links between the folding behavior of "real" proteins and theoretical models for protein folding.

Tea and coffee will be served in R3151 Beckman Institute at 2:15pm.

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