2026-06-30 カリフォルニア大学サンタバーバラ校（UCSB）
＜関連情報＞
- https://news.ucsb.edu/2026/022682/new-tools-study-protein-assembly-may-help-search-neurodegenerative-disease-therapeutics
- https://www.pnas.org/doi/10.1073/pnas.2531932123
アミロイド予測とLLPS予測：本質的に無秩序なプロテオームにおける相分離傾向の予測 amyloid-predict and LLPS-predict: Predicting phase separation propensities in the intrinsically disordered proteome
Samuel Lobo, Leif Griem, M. Scott Shell, and Joan-Emma Shea
Proceedings of the National Academy of Sciences Published:May 26, 2026
DOI:https://doi.org/10.1073/pnas.2531932123
Abstract
Amyloid formation and liquid–liquid phase separation (LLPS) are two important phenomena in cellular biology, linked to both normal physiological functions and various pathologies. Here, we present a computational framework that scores amyloid propensities (amyloid-predict) or LLPS propensities (LLPS-predict) from protein language model embeddings, enabling rapid proteome-wide annotation of peptides and residues. amyloid-predict achieves classification performance that exceeds existing AI and physics-based tools on a hexapeptide benchmark while enabling substantially faster high-throughput screening; notably, amyloid-predict is sensitive to subtle mutational effects and is influenced by sequence patterning and context rather than amino acid composition alone. We apply these protein language model classifiers to all the IDRs in the human proteome and uncover several protein categories with significant enhancement in amyloid and/or LLPS propensity, suggesting insights into the biological roles of these protein categories. For example, signaling receptors, carbohydrate-binding proteins, and Ca2+ binding proteins are enriched in aggregation propensity, while mRNA-binding proteins, ribonucleoprotein complex, and nuclear matrix proteins are enriched in LLPS propensity. Interestingly, we observe patterns of both high amyloid and LLPS propensity in several amyloid-forming and prionic proteins. Together, these results provide side-by-side landscapes of LLPS and amyloid potential across the disordered human proteome while offering a rapid screening tool for basic biology, disease-mechanism studies, and rational design of peptide therapeutics.
