100th Anniversary of Macromolecular Science Viewpoint: Data-Driven Protein Design

The design of synthetic proteins with the desired function is a long-standing goal in biomolecular science, with broad applications in biochemical engineering, agriculture, medicine, and public health. Rational de novo design and experimental directed evolution have achieved remarkable successes but are challenged by the requirement to find functional "needles" in the vast "haystack" of protein sequence space. Data-driven models for fitness landscapes provide a predictive map between protein sequence and function and can prospectively identify functional candidates for experimental testing to greatly improve the efficiency of this search. This Viewpoint reviews the applications of machine learning and, in particular, deep learning as part of data-driven protein engineering platforms. We highlight recent successes, review promising computational methodologies, and provide an outlook on future challenges and opportunities. The article is written for a broad audience comprising both polymer and protein scientists and computer and data scientists interested in an up-to-date review of recent innovations and opportunities in this rapidly evolving field.