Mechanism of Protein Denaturation - Guanidine Hydrochloride Induced Dissociation of Inhibitor-Protease Complexes

Document Type


Document Subtype


Presentation Date

Spring 3-5-2011

Conference Name

126th Annual Meeting of Indiana Academy of Science

Conference Location



Proteins perform their function in their native folded state. The native folded state of a protein is stabilized by hundreds of weak non-covalent interactions involving the peptide bonds and amino acid side chains of the protein. Certain chemicals inside the cell called osmolytes also play an important role in the stability of proteins. Understanding the molecular basis of the stability of native folded state and the molecular basis of the action of osmolytes on protein stability is one of the most extensively investigated research area in protein chemistry. Due to lack of appropriate protein systems, the investigations are mostly based on model compound studies. Our extensive research work on the association of protein inhibitors with serine proteases has shown that non-covalent interactions stabilizing inhibitor-protease complex are remarkably similar to interactions involved in the stabilization of native protein structure. In this research project I propose to use inhibitor-protease association as a model to study the molecular basis of the influence of osmolytes on protein stability. The research work would involve measurements of association equilibrium constants of inhibitor variants with a serine protease, bovine chymotrypsin, in the presence of different concentrations of osmolytes such as trimethylamine oxide, urea and glucose. The results of this investigation are expected to make important contribution in our understanding of the role of individual amino acid side chains in protein stability.


Proteases, Inhibitors, Denaturation, Proteins, Osmolytes


Chemistry | Life Sciences

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