Our progam explores how atomic motion and organized protein structure within proteins contributes to enzymatic catalysis. We wish:
- To determine, via an integrated application of experiment and theory, the elements of protein structure that create specific dynamics that are part of enzymatic catalysis on all relevant timescales. We study how protein dynamics, particularly focused on the energy landscape of the Michaelis complex and motion of the promoting vibrations, is related to function and coupled to allostery and how this concept can be expanded to fully elucidate allosteric regulation of proteins. This presents a potential paradigm shift for protein and enzyme regulation via new drug action. In addition, a deeper understanding of transition state passage leaves us with the view that transition state inhibitors often do not function by "locking in" a specific structure, but rather by preserving dynamics at the transition state. We will investigate this new principle of strong inhibitor binding via dynamic preservation as a paradigm for enzyme function and inhibition.
- To use the understanding of how important functional dynamics are coded into the protein structure gained in the above as a means to manipulate them in order to modify protein function.
- Project 1. Protein architecture and the energy landscape of enzymes. Prof. Robert Callender. Albert Einstein College of Medicine.(The Callender Lab)
- Project 2: Dynamics in enzymatic catalysis and transition state analogue binding. Prof. Vern Schramm, Albert Einstein College of Medicine. (The Schramm Lab)
- Project 3: Protein architecture and enzyme dynamics on timescales from fs to ms. Prof. Brian Dyer, Emory University. (The Dyer Lab)
- Project 4: Enzyme design and protein dynamics. Prof. Steve Schwartz. (The Schwartz Lab)