David G. Gorenstein, Ph.D., Professor, Charles Marc Pomerat Distinguished Professor of Biological Sciences, Associate Dean of Research
Our work may be roughly divided into three
main areas of structural biology research: (1) development and applications
of NMR spectroscopy to biological systems, (2) computational biochemistry,
and (3) biomolecular design.
We have been interested in the development of biophysical and bioanalytical applications of NMR spectroscopy to probe the detailed chemical structure and dynamics of biological molecules. Multinuclear NMR of enzyme complexes, nucleic acids, nucleic acid-drug and carcinogen complexes, and nucleic acid protein complexes is being pursued. The laboratory is involved in new instrumentation and computer software development (including further development of a complete relaxation matrix program, MORASS). The laboratory includes state-of-the-art 400 MHz, 600 MHz and 750 MHz NMR spectrometers.
We are studying the detailed solution structure and dynamics of various DNA binding proteins, such as lac repressor headpiece, 434 repressor (both helix turn helix proteins) and NF-IL6 (a basic leucine zipper). Triple resonance, multidimensional NMR is currently being carried out on these and various site-specific mutants with oligonucleotide duplexes. We are also using NMR and molecular dynamics calculations to define the structure and dynamics of other DNA and RNA binding proteins and their oligonucleotide complexes. This includes the HIV-1 nucleocapsid (NCp7), HIV-1 RNAse H and human beta-polymerase.
We also have a major program oriented toward the combinatorial selection, rational design, synthesis and structural characterization of oligonucleotide analogues (especially dithiophosphate analogues) and other agents directed toward the AIDS virus and oncogenes (this includes antisense and aptamer oligonucleotides).
