De novo protein design is a powerful approach to solve problems in medicine and material science. However, functional de novo protein design is still in its infancy. We are unable to precisely design macromolecular assemblies, dynamics or waters at interfaces; sheets or long loops fail at very high rates, so helical topologies are primarily used. Current one-sided protein-protein binding requires a prebuilt set of scaffolds and can only bind a small subset of natural proteins at helical interfaces. My lab will overcome these challenges by developing new protein design algorithms.
Modern manufacturing was revolutionized by parts that could be used interchangeably and easily connected to one another. We will apply this concept to engineer stimuli responsive macromolecular assemblies. Protein origami will pave the way toward broadly neutralizing vaccines, tissue regeneration, immune modulation, lithography masks and protein machines.
An ideal biosensor can accurately and continuously track a wide variety of pathogens, cancer biomarkers and small molecules. We will work to achieve this through computational design and integration with bioelectronics.
The ability to design enzymes completely computationally would be an invaluable tool for industry and academia. Existing technology require multiple steps of directed evolution to optimize enzyme activity.