Designing a New Diels Alderase: A Combinatorial, Semirational Approach Including Dynamic Optimization

This article illuminates a combinatorial approach to the design of enzymes that catalyze Diels-Alder reactions. We have seen from Siegel et al. that computational design of the Diels-Alder reaction is viable. This paper seeks to improve the catalytic efficiency of the Diels-Alder design, DA_20_00 Siegel et al., through molecular modeling, molecular docking, and density functional theory. The computational screening method used optimizes the substrate and enzyme simulataneously. In contrast to the Siegel et al. approach, a predesigned active sight is not incorporated into an existing protein fold; limiting mutations. These two approaches provide greater insight into de novo Diels-Alder design.