Funneling modulatory peptide design with generative models: Discovery and characterization of disruptors of calcineurin protein-protein interactions.

ABSTRACT: Design of peptide binders is an attractive strategy for targeting "undruggable" protein-protein interfaces. Current design protocols rely on the extraction of an initial sequence from one known protein interactor of the target protein, followed by in-silico or in-vitro mutagenesis-based optimization of its binding affinity. Wet lab protocols can explore only a minor portion of the vast sequence space and cannot efficiently screen for other desirable properties such as high specificity and low toxicity, while in-silico design requires intensive computational resources and often relies on simplified binding models. Yet, for a multivalent protein target, dozens to hundreds of natural protein partners already exist in the cellular environment. Here, we describe a peptide design protocol that h

SUBMITTER: Tubiana J 

PROVIDER: S-EPMC9928118 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature