The overall goal of the research in our laboratory is to relate the three-dimensional structure and dynamics of proteins to their biological functions. We use techniques of X-ray crystallography and other biophysical methods to elucidate the molecular structures, dynamics, and functions of proteins. Extensive use is made of modern computational methods to analyze the structures and their dynamics.
One project we have underway is directed towards obtaining an atomic description of the basis for binding of oxygen and other ligands to heme proteins. Detailed three-dimensional structures are being determined for modified myoglobins and hemoglobins and other novel heme proteins, such as nitrobindin, a protein we discovered that reversibly binds nitric oxide and is found throughout the animal kingdom.. We are also working to develop new techniques for observing the dynamics of proteins and nucleic acids using diffuse X-ray scattering analysis and molecular dynamics simulations. The result will be a transition from "snapshots" of macromolecules to the generation of "movies" of molecules in action.
Organisms have proteins that are highly adapted to the growing conditions in the environment. We have determined structures of enzymes from hyperthermophilic bacteria to reveal aspects of the connections of protein structure to dynamics, which is an integral part of proteins' designs. We have also developed new methods of improving the thermostability of proteins for potential commercial improvements.
Members of the laboratory are also involved in the field of structural genomics, the solving of structures whose function may not yet be known. The structures often give clues about the functions. We are currently working on structures of enzymes involved in natural product biosynthesis in order to help produce lead compounds for cancer pharmaceutical discovery. More recently, members of my laboratory have become involved in the Great Lakes Bioenergy Research Center, whose mission is to contribute basic science results to the development of biofuel, particularly cellulosic ethanol.
A longstanding interest in the laboratory is also computational biology. This activity entails the development and application of modern algorithms from computer science and applied mathematics to solve interesting biological problems.
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Statement of research interests: The overall goal of the research in my laboratory is to relate the three-dimensional structure and dynamics of proteins to their biological functions. We develop and we use techniques of X-ray crystallography and other biophysical methods to elucidate the molecular structures, dynamics, and functions of proteins. Extensive use is made of modern computational methods to analyze the structures and their dynamics. A variety of different biological systems are currently under study, including heme proteins, the enzyme adenylate kinase, cellulases, cellulose synthase, enzymes of natural product biosynthesis, collagen-modifying enzymes and structural genomic targets.