'Lubricating'the Folding Process: A Hydration Study

Johns Hopkins University, Baltimore MD

Investigators

Abstract

The sum of the biological reactions and processes within an organism is effected by proteins, or complexes of proteins with other biomolecules. Determination of a protein's three dimensional structure or fold, is fundamental to elucidating biological form and function. A detailed description of the folding process, the energetics of folding, and the energetics of protein - biomolecule interactions provides valuable insight in understanding the molecular bases of diseases caused by mutant proteins with aberrant functions, and the design of potential targets and gene therapies. There is a large body of evidence which indicates that changes in the hydration state of a protein is a key determinant of the folding process. Using Staphylococcal nuclease as a model system, I propose to study hydration-driven structural changes via a new high pressure X-ray crystallographic technique, and fluorescence and NMR spectroscopy.