The purpose of this project is to study the physical properties of a wide variety of biological macromolecules, with the goal of correlating these properties to the structure and function of the macromolecules. The emphasis is on the thermodynamics of the interactions of these macromolecules and on their molecular size and shape. Analytical ultracentrifugation and mathematical modeling are the principal research techniques used. Studies on HIV reverse transcriptase have been directed toward investigating the thermodynamics of the homogeneous association of the P66 subunit, and the heterogeneous association of P66 with the P51 subunit. Studies on chromagranin A have been directed toward determining the domain of this protein responsible for aggregation, and investigating the effects of pH and calcium ion concentration on the thermodynamics of the aggregative properties of a peptide encompassing this domain. Studies on CEB-63 and CEB-35, leucine-zipper peptides, have been directed toward determining the thermodynamic parameters characterizing their reversible aggregation. Studies on heat shock proteins and nucleic acids have been directed toward investigating the nature of their interactions. Studies on the interaction of HIV-1 RNA with nucleocapsid protein have been directed toward a more quantitative understanding of this interaction. Studies on the beta amyloid peptide have been directed toward understanding the aggregative properties of this peptide and its possible relationship to Alzheimer's disease.
