The Protein Design Archive (PDA): insights from 40 years of protein design

Abstract

While natural proteins are incredibly diverse biomacromolecules, they present only a subset of the sequence and structural space that is chemically possible¹. The field of protein design has the potential to illuminate the unexplored regions of this space, to deepen our understanding of sequence–structure–function relationships, and to enable the development of novel proteins that could be used to address societal challenges.

Protein design has evolved dramatically over the past 40 years from rational design to contemporary data-driven approaches. The field has now reached milestones such as the design of small-molecule² and protein³ binders, entirely novel folds^4,5,6, and has been recognized with a Nobel Prize. However, it can be difficult to identify current challenges and opportunities within the field as no easily searchable resource provides an overview of proteins that have been designed to date. Such a resource would improve our ability to learn from previous efforts and guide the development of future design methods.