Published August 23, 2026 08:00
Source https://doi.org/10.1021/acs.jcim.6c01376
We introduce a new computational tool (ACWF, Amyloid Coordinate Wizard Fibril) developed for analysis and visualization of 3D structures of amyloid fibrils. The presented hierarchical clustering method enables the classification of polymorphs into larger structural families and the identification of disease-specific structural differences. Beta-sheets segmented by arc motifs form the amyloid architecture - in these structures steric zippers ensure solvent exclusion. These complementary molecular surfaces were characterized by local values of three parameters, steric fit, area and interdigitation. Using these parameters, the amino acid residues forming structural hotspots were identified, displaying distinct patterns in each structural family. This framework provides a better understanding of how molecular-level interactions evolve into complex pathological formations, and how the zipper region changes locally as more compact structures emerge during the maturation of amyloids.
We publisher these results in the Journal of Chemical Information and Modeling. The database and wizard is available as a plugin for PyMol program, here (link).