ArticleChemical science2021
Covalent flexible peptide docking in Rosetta.
Article in Chemical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Substrate-Derived Peptides for Selective Covalent Inhibition of Protein Tyrosine Kinases.ACS chemical biology · 2026Article
- In silico identification of selective cyclodecapeptide inhibitors targeting Plasmodium falciparum Grp78 chaperone.Journal of computer-aided molecular design · 2026Article
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- Structure-based rational design of covalent probes.Communications chemistry · 2025Review
- Computational Design of Lysine Targeting Covalent Binders Using Rosetta.Journal of chemical information and modeling · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Artificial Intelligence Transforming Post-Translational Modification Research.Bioengineering (Basel, Switzerland) · 2024Review
- A Chemical Approach to Assess the Impact of Post-translational Modification on MHC Peptide Binding and Effector Cell Engagement.ACS chemical biology · 2024Article
- Optimizing Trilobatin Production via Screening and Modification of Glycosyltransferases.Molecules (Basel, Switzerland) · 2024Article
- Computational 3D Modeling-Based Identification of Inhibitors Targeting Cysteine Covalent Bond Catalysts for JAK3 and CYP3A4 Enzymes in the Treatment of Rheumatoid Arthritis.Molecules (Basel, Switzerland) · 2023Article
- A simple method for developing lysine targeted covalent protein reagents.Nature communications · 2023Article
- SARS-CoV-2 spike and ACE2 entanglement-like binding.Quantum machine intelligence · 2023Article
- Peptide-based covalent inhibitors of protein-protein interactions.Journal of peptide science : an official publication of the European Peptide Society · 2023Review
- Rapid Covalent Labeling of Membrane Proteins on Living Cells Using a Nanobody-Epitope Tag Pair.Bioconjugate chemistry · 2022Article
- VInternational journal of molecular sciences · 2022Review
- Rosetta FlexPepDock to predict peptide-MHC binding: An approach for non-canonical amino acids.PloS one · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Electrophilic peptides that form an irreversible covalent bond with their target have great potential for binding targets that have been previously considered undruggable. However, the discovery of such peptides remains a challenge. Here, we present Rosetta CovPepDock, a computational pipeline for peptide docking that incorporates covalent binding between the peptide and a receptor cysteine. We applied CovPepDock retrospectively to a dataset of 115 disulfide-bound peptides and a dataset of 54 electrophilic peptides. It produced a top-five scoring, near-native model, in 89% and 100% of the cases when docking from the native conformation, and 20% and 90% when docking from an extended peptide conformation, respectively. In addition, we developed a protocol for designing electrophilic peptide binders based on known non-covalent binders or protein-protein interfaces. We identified 7154 peptide candidates in the PDB for application of this protocol. As a proof-of-concept we validated the protocol on the non-covalent complex of 14-3-3σ and YAP1 phosphopeptide. The protocol identified seven highly potent and selective irreversible peptide binders. The predicted binding mode of one of the peptides was validated using X-ray crystallography. This case-study demonstrates the utility and impact of CovPepDock. It suggests that many new electrophilic peptide binders can be rapidly discovered, with significant potential as therapeutic molecules and chemical probes.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.