Protein-Peptide Docking with ESMFold Language Model

Abstract

Designing peptide therapeutics requires precise peptide docking, which remains a challenge. We assessed the ESMFold language model, originally designed for protein structure prediction, for its effectiveness in protein-peptide docking. Various docking strategies, including polyglycine linkers and sampling-enhancing modifications, were explored. The number of acceptable-quality models among top-ranking results is comparable to traditional methods and generally lower than AlphaFold-Multimer or Alphafold 3, though ESMFold surpasses it in some cases. The combination of result quality and computational efficiency underscores ESMFold’s potential value as a component in a consensus approach for high-throughput peptide design.