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

The field of protein design has changed dramatically over the last 40 years, with a range of methods developing from rational design to more recent data-driven approaches. While considerable insight could be gained from analysing designed proteins, there is no single resource that brings together all the relevant data, making it difficult to identify current challenges and opportunities within the field. Here we present the Protein Design Archive, a website and database of designed proteins. Using the database, we performed systematic analysis that reveals a rapid increase in the number and complexity of designs over time and uncovers biases in their amino-acid usage and secondary structure content. Finally, sequence- and structure-based analysis demonstrates the breadth and novelty of designs within the archive. The PDA will be a valuable resource for guiding development of protein design, helping the field reach its potential. The PDA is available freely and without registration at https://pragmaticproteindesign.bio.ed.ac.uk/pda/.