PepNN: a deep attention model for the identification of peptide binding sites
Open accessPublished version of a preprint
Abstract
Protein-peptide interactions play a fundamental role in many cellular processes, but remain underexplored experimentally and difficult to model computationally. Here, we present PepNN-Struct and PepNN-Seq, structure and sequence-based approaches for the prediction of peptide binding sites on a protein. A main difficulty for the prediction of peptide-protein interactions is the flexibility of peptides and their tendency to undergo conformational changes upon binding. Motivated by this, we developed reciprocal attention to simultaneously update the encodings of peptide and protein residues while enforcing symmetry, allowing for information flow between the two inputs. PepNN integrates this module with modern graph neural network layers and a series of transfer learning steps are used during training to compensate for the scarcity of peptide-protein complex information. We show that PepNN-Struct achieves consistently high performance across different benchmark datasets. We also show that PepNN makes reasonable peptide-agnostic predictions, allowing for the identification of novel peptide binding proteins.
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- Authors
- Abdin, O., Nim, S., Wen, H., & Kim, P. M.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Kim, Philip M.
- Venue
- Communications Biology
- Published
- 2022-05-26
- Volume
- 5
- Issue
- 1
- Pages
- 503-503
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC9135736
- OpenAlex
- W4281557145
- Cited by
- 104
- References
- 10
- Citations by year
- 2026: 22 · 2025: 37 · 2024: 24 · 2023: 12 · 2022: 5 · 2021: 4
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (RGPIN-2017-064)
- Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (PJT-166008)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- protein-peptide interactions, graph neural networks, transfer learning, peptide conformational flexibility
- MeSH terms
- Binding Sites, Peptides, Proteins, Neural Networks, Computer
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