Computational design of protein–protein interactions

Abstract

A long-term aim of computational design is to generate specific protein-protein interactions at desired affinity, specificity, and kinetics. The past three years have seen the first reports on atomically accurate de novo interactions. These were based on advances in design algorithms and the ability to harness high-throughput experimental characterization of design variants to optimize binding. Current state-of-the-art in computational design lacks precision, and therefore requires intensive experimental optimization to achieve parity with natural binders. Recent successes (and failures) point the way to future progress in design methodology that would enable routine and robust design of binders and inhibitors, while also shedding light on the essential features of biomolecular recognition.