Our research combines nuclear magnetic resonance (NMR) spectroscopy with Biophysics, Biochemistry, and Chemistry to investigate cellular processes at the molecular and atomic levels in relation to human disease. We presently focus on two areas in biology: Gene Regulation and HIV pathogenesis. In order to understand how biological macromolecules work and intervene in a rational manner with respect to activity and function, detailed knowledge of their architecture and dynamic features is required. Evaluation of the major determinants for stability and conformational specificity of normal and disease-causing forms of these molecules, will allow us to unravel the complex processes associated with disease.
Our group has developed new NMR methods for determining three-dimensional structures of biological macromolecules and applied these to challenging system. Key contributions include the development of restrained molecular dynamics/simulated annealing algorithms and multidimensional, heteronuclear spectroscopy, which allowed the extension of conventional NMR methods to higher molecular weight systems. The Gronenborn group has solved solution structures of a large number of medically and biologically important proteins, including cytokines and chemokines, transcription factors and their complexes and various HIV and AIDS related proteins. Work is also carried out on protein folding and design using the model protein GB1.