Rational protein engineering using an omni-directional multipoint mutagenesis generation pipeline.

ABSTRACT: Generative models have transformed protein design by enabling the generation of extensive datasets. However, accurate identification of biologically active sequences with specific functions within such data remains a significant challenge. In this study, we present a novel pipeline that integrates models for sequence generation, ranking, and selection to engineer proteins with enhanced properties. Our Omni-Directional Multipoint Mutagenesis (ODM) generation model was developed by refining a pre-trained protein BERT model to produce 100,000 mutant proteins. To evaluate the effects of mutations on protein activity, we utilized the lowest probability prediction across all masked positions as an indicator to rank the mutant sequences. Furthermore, we developed thermostability models to identif

SUBMITTER: Fan L 

PROVIDER: S-EPMC12392658 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature