The Programmable Biology Group

We are developing peptide-guided protein therapeutics to target disordered and "undruggable" proteins. To accomplish this goal, we train generative language models, such as SaLT&PepPr, PepPrCLIP, and PepMLM, to de novo design peptide binders to any pathogenic protein without needing its structure, and subsequently link these binders to post-translational modification domains to edit the protein. Our current peptide-E3 ubiquitin ligase (uAbs) and peptide-deubiquitinase fusions (duAbs) represent a CRISPR-like approach for targeted protein degradation and stabilization. We are now extending this to multi-objective-guided generation of therapeutic peptides with PepTune and specific targeting of dysregulated isoforms with PTM-Mamba, FusOn-pLM, and moPPIt!