(305d) Computationally-Designed 10th Type III Fibronectin Domains for Peptide Binding

Proteins are the fundamental building blocks of all living organisms. They perform a variety of functions within organisms such as providing cellular structural support, catalyzing an array of metabolic reactions, helping in DNA replication, and enabling molecular transport. The roles and methods through which proteins regulate the various processes of life have been a pivotal research focus in the fields of proteomics and medical science for decades. Within the last year, Alpha-Fold 2 proved that the rules of protein structures are sufficiently well understood that can be predicted from scratch. Now, the field of computational protein engineering and design needs to develop a comparable level of understanding of protein-protein interactions.

Our research group developed an Algorithm for Ultra-rapid Binding Interaction Engineering (AUBIE) for the quick de novo design of binding proteins. The key focus of the algorithm is in the targeted placement of optimal hotspot interactions to enable high affinity binding. We have used AUBIE to design 10^th Type III Fibronectin domains to bind the signaling peptides HA, FLAG and MYC. This presentation will briefly describe AUBIE before discussing the qualities and features of the predicted designs, culminating in a description of how these methods can be expanded to enable the on-demand design of protein-protein interfaces.