PepMLM: Target Sequence-Conditioned Generation of Therapeutic Peptide Binders via Span Masked Language Modeling.

ABSTRACT: Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as pharmacological alternatives, but still require small molecule docking at binding pockets for targeted protein degradation. The computational design of protein-based binders presents unique opportunities to access "undruggable" targets, but have often relied on stable 3D structures or structure-influenced latent spaces for effective binder generation. In this work, we introduce PepMLM, a target sequence-conditioned generator of de novo linear peptide binders. By employing a novel span masking strategy that uniquely positions cognate peptide seque

SUBMITTER: Chen T 

PROVIDER: S-EPMC10593082 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature