Step-by-step design of proteins for small molecule interaction: A review on recent milestones

Abstract

Protein design is the field of synthetic biology that aims at developing de novo custom-made proteins and peptides for specific applications. Despite exploring an ambitious goal, recent computational advances in both hardware and software technologies have paved the way to high-throughput screening and detailed design of novel folds and improved functionalities. Modern advances in the field of protein design for small molecule targeting are described in this review, organized in a step-by-step fashion: from the conception of a new or upgraded active binding site, to scaffold design, sequence optimization, and experimental expression of the custom protein. In each step, contemporary examples are described, and state-of-the-art software is briefly explored.