The Structural Biology Core will be a shared central resource to enable researchers at the University of Pennsylvania to bring molecular and structural analysis and understanding to their research projects on AIDS- related macromolecules. Molecular mechanism, molecular structure and drug design all are subjects of currently funded research at the University. They also are common themes in several upcoming projects. A common need in these projects as well as those on the biology of AIDS-related macromolecules is to enable the use of structural biology approaches in order to learn more about structure and mechanism and to use that information for structure- and mechanism-based antagonist design. The goal of the Structural Biology Core will be to provide services which facilitate the use of structural biology to solve AIDS-related research problems. The four main functions of the Structural Biology Core will be: (1) Protein Production, including scaled up expression and purification to provide materials for structural and mechanistic studies; (2) Interaction Analysis, focusing on optical biosensor analysis of macromolecular interaction kinetics and characterization of assembly mechanisms in HIV-1 and the pathogenesis of AIDS; (3) Structure-Function Analysis, including molecular graphics visualization of high resolution structures and structural guidance for mutagenic analysis; and (4) Resource Networking, in particular guiding users to technology resources beyond the Core for specialized biophysical, computational and high resolution structure determination. A key strength of the CFAR at the University of Pennsylvania will be to bring together researchers investigating the biology and chemistry of immunodeficiency viruses and AIDS with the resources to elucidate molecular and structural properties and to use these properties as lead information in drug design. Coordinated research and collaborations will be encouraged amongst biologists, chemists and structural biologists. The Structure Biology Core will provide a centralized resource which will provide protein materials, initiate interaction analyses and structure-function studies, facilitate and lead AIDS-related projects into the structural biology area and hence help meet the molecular, structural and drug design goals of AIDS research at UPenn.