De novo protein fusions as platforms for enzyme design

Abstract

Control over enzymatic catalysis is a central goal of biotechnology. Recent advances in computational protein design are beginning to allow for the de novo creation of arbitrary protein structures, but the design of arbitrary functions that match or exceed those found in nature remains extremely challenging. To help advance towards this demanding goal, I have designed de novo multidomain proteins based on one of the most common and catalytically diverse enzyme architectures known. These TIM-barrel fusion proteins remain folded at high temperatures and concentrations of denaturant and are highly mutable, and can thus serve as platforms for rational enzyme design.