MoPPIt: <i>De Novo</i> Generation of Motif-Specific Binders with Protein Language Models.

ABSTRACT: The ability to precisely target specific motifs on disease-related proteins, whether conserved epitopes on viral proteins, intrinsically disordered regions within transcription factors, or breakpoint junctions in fusion oncoproteins, is essential for modulating their function while minimizing off-target effects. Current methods struggle to achieve this specificity without reliable structural information. In this work, we introduce a motif-specific PPI targeting algorithm, moPPIt, for de novo generation of motif-specific peptide binders from the target protein sequence alone. At the core of moPPIt is BindEvaluator, a transformer-based model that interpolates protein language model embeddings of two proteins via a series of multi-headed self-attention blocks, with

SUBMITTER: Chen T 

PROVIDER: S-EPMC11312608 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature