PACT - Prediction of Amyloid Cross-interaction by Threading

• DOI: 10.1101/2022.07.07.499150
• Publication Date: 2022-07-10T21:20:12Z
• Authors: Jakub W. Wojciech...; Witold Szczurek; Natalia Szulc; Monika Szefczyk; Malgorzata Kotulska
• Keywords: Pact; Amyloid (mycology); Human proteins; Protein Stability; Threading (protein sequence); Amyloid disease

ABSTRACT Amyloids are protein aggregates usually associated with their contribution to several diseases e.g., Alzheimer’s and Parkinson’s. However, they also beneficially utilized by many organisms in physiological roles, such as microbial biofilm formation or hormone storage. Recent studies showed that an amyloid aggregate can affect aggregation of another protein. Such cross-interactions may be crucial for understanding the comorbidity influence amyloids on human amyloidogenic proteins. due demanding experiments, interaction phenomena is still limited. Moreover, no dedicated computational method predict potential interactions has been available until now. Here, we present PACT - a prediction cross-interactions. The based modeling heterogenous fibril formed two peptides. stability resulting structure assessed using statistical approximates energetic model. Importantly, work long fragments and, purely physicochemical approach, it relies very little training data. was evaluated data collected AmyloGraph database achieved high values AUC (0.88) F1 (0.82). new opens possibility throughput interactions. We used study CsgA, bacterial from species inhabiting intestines, Alpha-synuclein which involved onset Parkinson’s disease. show correctly predicted interactions, performing experimental validation, highlighted importance specific regions both tool web server at: https://pact.e-science.pl/pact/ . local version downloaded from: https://github.com/KubaWojciechowski/PACT