AlphaFold models of host-pathogen interactions elucidate the prevalence and structural modes of molecular mimicry.

ABSTRACT: Pathogens exploit host cellular machinery through protein-protein interactions (PPIs), often using molecular mimicry to hijack host cellular processes. While there have been thousands of host-pathogen PPIs determined to date, the lack of structural information for these impedes the study of the prevalence of molecular mimicry and convergent evolution of protein interaction interfaces. To address this, we benchmarked AlphaFold2 and 3 for prediction of structures of host-pathogen interactions observing that accurate models can be retrieved when ranking by modelling confidence, despite an overall low performance. We predicted structures for 6,782 pathogen-human PPIs yielding 803 models of higher confidence. Most pathogen proteins interacting with a common human protein are predicted to do so

SUBMITTER: Baptista D 

PROVIDER: S-EPMC12258915 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature