Molecular de-extinction of ancient antimicrobial peptides enabled by machine learning.

ABSTRACT: Molecular de-extinction could offer avenues for drug discovery by reintroducing bioactive molecules that are no longer encoded by extant organisms. To prospect for antimicrobial peptides encrypted within extinct and extant human proteins, we introduce the panCleave random forest model for proteome-wide cleavage site prediction. Our model outperformed multiple protease-specific cleavage site classifiers for three modern human caspases, despite its pan-protease design. Antimicrobial activity was observed in vitro for modern and archaic protein fragments identified with panCleave. Lead peptides showed resistance to proteolysis and exhibited variable membrane permeabilization. Additionally, representative modern and archaic protein fragments showed anti-infective efficacy against A. baumannii

SUBMITTER: Maasch JRMA 

PROVIDER: S-EPMC11625410 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature