Funds are requested for a high sensitivity microcalorimeter with capabilities for differential scanning calorimetry and isothermal titration calorimetry under the NCRR Shared Instrumentation Grant Program. This microcalorimeter will be placed in a Biomolecular Recognition Core Facility where it will be available to the major users listed below and members of their laboratories, and as time permits, to other faculty in the University. The University of Michigan presently lacks instrumentation for high sensitivity differential scanning calorimetry and has no instrument capable of isothermal titration calorimetry. Thus the requested equipment will provide entirely new capabilities for a broad spectrum of NIH-funded faculty members in the Departments of Biological Chemistry, Biophysics, and Chemistry. The equipment will be used to obtain thermodynamic information on macromolecules and their interactions with ligands that will complement ongoing structural and mechanistic characterizations of proteins, oligosaccharides and oligonucleotide. A major use of the requested equipment will be to assess the energetic implications of conformational transitions and local interactions in proteins. Interactions between proteins and their ligands, including carbohydrates and oligonudeotides, will also be studied using isothermal titration calorimetry. Finally, differential scanning calorimetry will be used to study the thermal denaturation and renaturation of proteins and oligonucleotide. The ability to use calorimetric techniques will greatly strengthen the ability of the major users to address problems currently under study in their laboratories, and the sponsorship of a short course in microcalorimetry by the Initiative in Biomolecular Recognition will provide training opportunities in microcalorimetry for these faculty and their students and fellows.
