2024 AIChE Annual Meeting
(394a) Polymerized Amyloids: Sequence and Structure Space of Tandem Repeat Proteins
Authors
Jin, T. - Presenter, University of Wisconsin-Madison
Coley, C., MIT
Alexander-Katz, A., Massachusetts Institute of Technology
Amyloids are highly ordered cross-β protein aggregates that have traditionally been associated with neurodegenerative diseases. Recent research underscores their potential in the realm of functional materials based on their unique repetitive structures, high stability, and self-assembling capabilities. Leveraging advancements in protein structural prediction tools, our study explores tandem sequence designs to achieve varied aggregation morphologies with high in silico structural confidence, facilitated by machine learning-driven evolution. We present a robust approach that promotes amyloid β-42 aggregation into β-solenoid-like structures through the polymerization of amyloid segments with a random peptide linker. Employing the AlphaFold model allows us to screen linker sequences efficiently, ensuring high structural confidence. Our methodology extends to rapidly explore the tandem sequence space using a genetic algorithm and develop a surrogate model of sequences-to-structural confidence predictions based on large language model. This approach not only yields β-solenoid structures but also enables the design of single-layer β-sheets along the evolutionary pathway. Our work provides new insights on amyloid aggregation, functional amyloid-based materials and protein scaffold designs.