The overall objective of this proposal is to contribute to a basic understanding of the functional properties of biological macromolecules as revealed in accurate atomic models. Such models are significant for the generation and testing of hypotheses directly related to biological action in diverse systems. Diffraction studies on crystals can provide detailed and comprehensive structural information on proteins and other macromolecules, and multidimensional NMR spectroscopy is emerging as an alternative source of such information. It is important that the atomic models derived from these experiments be defined as accurately as possible. Dr. Hendrickson is seeking here to develop methods for optimizing the accuracy of experimentally determined atomic models, to apply these refinement methods to specific biochemical problems, and to analyze in detail the structural and dynamic properties of the resulting models. In particular, (1) he will refine a number of significant biological macromolecules against x-ray diffraction data, and analyze the structural and dynamic properties of the resulting models, (2) he will identify attributes that characterize reliably determined structures, (3) he will attempt to enhance the efficiency and convenience of crystallographic refinement procedures, (4) he will strive to develop appropriate treatments for dynamic properties in crystal, (5) he will extend the method of stereochemically restrained refinement to problems in 2D NMR spectroscopy, and (6) he will continue to maintain and distribute a system of refinement programs.
