Research Statement

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The long-range goal of research in the Goldenberg laboratory is to understand the role of protein dynamics in determining the stabilities of protein structures, the specificity of their formation and their functional properties. Our current efforts are focused on two aspects of protein dynamics. The first is the characterization of unfolded proteins, which are now recognized to play important roles in vivo. We are particularly interested in determining how the properties of unfolded proteins change in response to solution conditions and the presence of high concentrations of other macromolecules, as found intracellularly. The second focus of our work is the interaction between a protease, trypsin, and a natural inhibitor of this enzyme, bovine pancreatic trypsin inhibitor (BPTI). BPTI is a member of a large class of natural protease inhibitors that act by binding to the active sites of their targets, much as a substrate would, but are resistant to hydrolysis. We believe that the rigidity of the enzyme-inhibitor complex is key to preventing the catalytic reaction, and we are currently using NMR spectroscopy, thermodynamic and kinetic measurements and x-ray crystallography to learn more about the factors that determine flexibility in the context of an enzyme-substrate complex and about the nature of the motions that are necessary for catalytic function.

Research Interests

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General Interests

• Biochemistry & Structural Biology

Specific Interests

• Protein folding and dynamics
• Unfolded proteins
• Serine proteases and their inhibitors
• NMR spectroscopy