The purpose of this project is the collaborative study of the physical properties of a wide variety of biological macromolecules with the goal of correlating these properties with the structure and function of the macromolecules. Analytical ultracentrifugation and mathematical modeling are the principal research techniques used. One of the areas of major emphasis was a set of collaborative studies of proteins involved in DNA transcription initiation and in DNA repair. The investigations with the laboratory of Dr. Wilson on homogeneous and heterogeneous interactions of DNA Ligase I and Polymerase beta were brought to a successful conclusion. Three new studies in this area are in progress: 1) on the interactions between DNA Ligase I and the replication protein, proliferating cell nuclear antigen (PCNA), in collaboration with Dr. Wilson and Dr. Tomkinson; 2) on interaction mechanisms between the XRCC1(1-183) protein and DNA polymerase-beta and its subdomains, in collaboration with Dr. Wilson and Dr. Mullen; and 3) the study of DNA transcription initiation repression by gal repressor (galR) and the HU protein, in collaboration with Dr. Adhya's laboratory. Other areas of high activity of the Resource were the characterization of homogeneous and heterogenous reversible interactions of a series of different T-cell membrane receptor fragments, in collaboration with the laboratory of Dr. Margulies, and of the interactions of three Herpes simplex virus capsid proteins, in collaboration with the Drs. Brown, Steven and Newcomb. Further collaborative projects of the Resource on the characterization of reversible interactions include the investigation of the chain of interactions which lead to the formation of the hypusine residue in the iIF-5A protein. A first part of this study in collaboration with Dr. Wolff has been successfully completed, and experiments to clarify additional aspects of these interactions are planned. Research on the cell cycle regulatory protein p53 with members of Dr. E. Appella's laboratory has continued with investigations of the interactions of carboxyterminal domain of p53 with casein II kinase, and of the interaction of p53 DNA-binding domain with DNA. Similarly, collaborations with the same laboratory on p7 nucleocapsid interaction with RNA and with HIV-I integrase have started. (This is a continuation of Intramural Research Project Z01-RR-10184-14 BEI.)