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 sizes and shapes. Analytical ultracentrifugation and mathematical modeling are the principal research techniques used. Studies on DNA polymerase beta have involved the structure of this molecule as revealed by fluorescence and hydrodynamic behavior. Studies on chromagranin A have been directed toward investigating the thermodynamics of the interaction with the intraluminal loop of the inositol 1,4,5-triphosphate receptor of the chromaffin cell secretory vesicle. Studies on the interaction of HIV-1 RNA with nucleocapsid protein involve determining the stoichiometry and association constants that characterize the interactions, and the domains of the protein and RNA that are responsible for these interactions. Studies on p53 have been directed toward determining the relationship of the primary structure of the tetramerization domain to the thermodynamics of the self-association, and to studying the thermodynamics of the association of DNA with the DNA-binding domain. Studies on IgG binding have been directed toward understanding the interaction of cell surface glycoproteins and antibodies. Studies on polymethacrylic acid have been directed toward understanding the effect of electrostatic charge on the behavior of biologically important molecules.
