Heat shock proteins (Hsp) comprise a group of ubiquitous polypeptides whose expression is induced when cells are subjected to stressful conditions such as increasing temperatures, high pressures, or toxic compounds. The induction of Hsp correlates with the abundance of unfolded polypeptide chains, which suggest a protective physiological role for these proteins. Their activity involves a chaperone-like behavior that helps the correct folding of nascent polypeptide chains by binding to exposed hydrophobic residues. Hsp are involved in the assembly and disassembly of multimeric protein structures, the translocation of proteins across membranes, and the secretion and degradation of proteins. Hsp also stimulate protein glycosylation. Although the stress response is well documented in a wide range of organisms, its regulation and molecular mechanism are presently not very clear.

The ultimate objective of this research is to define the mechanism of activity of Hsp including the modes of interaction of Hsp with substrates and regulatory proteins. The approach involves the use of computational techniques such as molecular dynamics simulation to complement biochemical and biophysical experiments. Dynamics simulations are being used to determine the conformational properties of the ATPase domain of Hsp70. These simulations are based on the X-ray structure of a 44 kD bovine brain recombinant protein solved at 1.7 angstroms resolution. A series of simulations are being performed in vacuum and in aqueous environment of the plain protein and the protein complexed with ATP and ADP, using the CHARMm force field. The motility of protein backbone atoms, side chain, secondary structure and protein sub-domains will be determined with statistical techniques. While the file preparation and analysis of the dynamics trajectories can be performed locally, the bulk of the simulation will be performed using facilities at the National Center for Supercomputer Applications at the University of Illinois. The data sets produced by the simulation are in the 50 –300 Mb range. Availability of Internet 2 connectivity would greatly facilitate the interaction with the NCSA computers.