Research in this laboratory is centered around solution studies on the structure and dynamics of proteins, protein-protein complexes and protein-nucleic acid complexes using multidimensional NMR spectroscopy, and on the development and application of novel NMR and computational methods to aid in these studies. Particular emphasis is being placed on complexes involved in signal transduction and transcriptional regulation, and on AIDS and AIDS-related proteins. Recent accomplishments include the extension of the applicability of the NMR method to structures larger than 40 kDa. Structures solved in the last year include phosphoryl transfer complexes of enzyme IIA(mannitol) + HPr, and enzyme IIA(glucose)enzyme IIB(glucose) of the PTS pathway, a complex between the KH3 and KH4 domains of FBP and a single stranded DNA 29mer derived from the FUSE element of the cmyc oncogene; and a comple of the KH3 domain of hnRNP K and a DNA 11mer derived from the CT element of the cmyc oncogene. Examples of methodological developments include the panoply of 3D and 4D heteronuclear NMR experiments that have been developed at the NIH and are essential for studying larger proteins whose overlapping resonances pose a formidable problem; methods that make use of anisotropy of the alignment tensor (e.g. residual dipolar couplings measured on macromolecules dissolved in dilute liquid crystalline media such as the nematic phases of rod-shaped virus particles) or the diffusion tensor (for highly non-spherical molecules) to provide long-range orientational information that is not available from other NMR parameters that rely entirely on close spatial proximity of atoms; and the development of fast and efficient algorithms for the analysis of NMR spectra and for the computation of three-dimensional structures based on all available experimental NMR restraints. Very recent developments include the use of rigid mody minimization and constrained/restrained simulated annealing to accurately dock protein-protein complexes on the basis of intermolecular NOE and dipolar coupling data.