Computational de-novo design of ester hydrolases

Abstract

Computational protein design is a relatively new technique used to devise amino acid sequences to fold into proteins having novel structures or functions. Here, we first give an overview about the approaches and algorithms used in computational protein design, together with examples of recently reported successful designs of protein structure and function. Then we present in-detail a computational algorithm for one specific application of computational protein design, namely the de-novo design of catalytic activity. Next, we apply this algorithm to design catalysts for ester hydrolysis. Several low-activity catalysts were obtained, highlighting both the potential and the challenges inherent in computational design. Finally, we introduce another novel computational procedure for the de-novo design of protein backbones that make specific required interactions.