Donald Hilvert

TL;DR: Using new algorithms that rely on hashing techniques to construct active sites for multistep reactions, retro-aldolases that use four different catalytic motifs to catalyze the breaking of a carbon-carbon bond in a nonnatural substrate are designed.

TL;DR: The design of enzymes that catalyze the bimolecular Diels-Alder reaction, a carbon-carbon bond formation reaction that is central to organic synthesis but unknown in natural metabolism, is described.

TL;DR: While nature evolved polypeptides over billions of years, protein design by evolutionary mimicry is progressing at a far more rapid pace, so intelligent libraries and improved search techniques are consequently important for future advances.

TL;DR: An iterative approach to computational enzyme design, including detailed MD and structural analysis of both active and inactive designs, promises a more complete understanding of the underlying principles of enzymatic catalysis and furthers progress toward reliably producing active enzymes.

TL;DR: By using a simple electrostatically based tagging system for protein encapsulation, HIV protease is sequestered within an engineered lumazine synthase capsid and the superior properties of the evolved capsid can be ascribed to multiple mutations that increase the net negative charge on its luminal surface and thereby enhance engineered Coulombic interactions between host and guest.