From Computational Design to a Protein That Binds

Researchers use computational approaches to design two proteins from scratch that bind to the flu virus. Protein-protein interactions are critical for many biological processes, and over the past several decades, this importance has prompted researchers to investigate the physical and chemical bases of protein binding. How much do we now understand about how proteins interact? Perhaps the most rigorous way to answer this question is to endeavor to design, at an atomic level of detail, such an interaction from scratch. On page 816 of this issue, Fleishman et al. (1) take on this challenge. They used a computational method that enabled them to design two proteins that bind to a preselected surface on an influenza virus. This work demonstrates how far we have come in understanding and being able to predict protein-protein interactions, and the technique could prove useful for developing biosensors, reagents, and more effective drugs.