Ivan Korendovych

Abstract Binding and catalysis play central roles in living systems. While natural proteins have finely tuned affinities for their primary ligands, they also bind weakly and promiscuously to other molecules, which serve as starting points for the incremental evolution of different specificities. Thus, modern proteins have emerged from the joint exploration of sequence and structural space.

Neurodegenerative diseases have a tremendous impact on the health of the global population with ∼ 24 million people diagnosed worldwide, and an estimated economic cost of $100 billion dollars a year in the USA alone.[1, 2] In many cases neurodegeneration is highly correlated with protein aggregation,[2-6] yet the biological function and toxicity mechanism of protein aggregates observed in the pathological state is not completely understood.[4, 5] Previously, we have discovered that...

Extended Data Fig. 1 Top scoring tripeptides. Top ranked tripeptides identified using the brute-force computational search on 8000 candidates. The score is based on the reward function rtri. Abbreviations: AP, aggregation propensity; logP; hydrophobicity. Source data Extended Data Fig. 2 Overall results for the synthesized pentapeptides.