Amyloid Explorer: a global atlas of amyloid fibril structures and thermodynamic principles

Abstract

Amyloid fibrils underpin both functional and pathological protein assemblies and exhibit extensive structural polymorphism. More than 600 high-resolution fibril structures are now available across over 50 protein sequences, yet comparative analysis has been hindered by fragmented resources and inconsistent annotation. Here we present Amyloid Explorer, an open-access platform that integrates the complete fibril archive into a standardized, quality-controlled, and thermodynamically annotated framework. Each entry includes residue- and segment-level stability maps, structural quality metrics, and interactive visualization tools. Global analysis across the dataset reveals conserved rules of amyloid assembly, including cooperative cores, framework polymorphism through reuse of conserved segments in distinct folds, polymorph-specific energetic anchors, and short frustration zones. By combining scale with accessibility, Amyloid Explorer transforms a static archive into a discovery platform for mechanistic insight, classification, and the design of aggregation modulators.