Abstract by Steven Jacobsen
Chemistry and Biochemistry
Guiding the Synthesis of Enzyme-Like Peptide Catalysts Using Computational Modeling
Nature's enzymes are among the most effective catalysts for biological and organic reactions. Enzymes achieve their efficiency through substrate binding and activation, proximity effects, transition state stabilization, and substrate preorganization. We are interested in mimicking these effects through the development of enzyme-like multifunctional catalysts. Using helical peptide scaffolds, we have developed bifunctional catalysts that achieve enzyme-like reactivity. Additionally, we have demonstrated that the structure of a peptide scaffold can influence both reaction rate and enantioselectivity in organic reactions, making it essential to rationally design our catalysts. In order to accelerate the development of new and more efficient peptide-based scaffolds, we are using computational modeling to simulate reactions and focus on the most promising catalyst structures. The combination of modeling and experimental results is enabling us to identify and design new enzyme-like catalysts with the ideal structures for cooperative catalysis.