ArticleProceedings of the National Academy of Sciences of the United States of America2017
Discovery of peptide ligands through docking and virtual screening at nicotinic acetylcholine receptor homology models.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
- Cyclic Peptides as Modulators of Protein-Protein Interactions: A Survival Guide from Discovery Platforms to AI-Driven Design.International journal of molecular sciences · 2026Review
- A deep learning framework (CreoPep) for target-specific design and optimization of conotoxin peptides.Communications chemistry · 2026Article
- Article
- Harnessing Deep Learning Methods for Voltage-Gated Ion Channel Drug Discovery.Physiology (Bethesda, Md.) · 2025Review
- In Silico Conotoxin Studies: Progress and Prospects.Molecules (Basel, Switzerland) · 2024Review
- Virtual Screening of Peptide Libraries: The Search for Peptide-Based Therapeutics Using Computational Tools.International journal of molecular sciences · 2024Review
- Targeting Dysregulated Ion Channels in Liver Tumors with Venom Peptides.Molecular cancer therapeutics · 2024Review
- Computational Design of α-Conotoxins to Target Specific Nicotinic Acetylcholine Receptor Subtypes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- A practical guide to machine-learning scoring for structure-based virtual screening.Nature protocols · 2023Review
- PD1 CD44 antiviral peptide as an inhibitor of the protein-protein interaction in dengue virus invasion.Peptides · 2022Article
- Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications.Biomolecules · 2022Review
- An Overview of Antiviral Peptides and Rational Biodesign Considerations.Biodesign research · 2022Review
- High-Throughput Prediction and Design of Novel Conopeptides for Biomedical Research and Development.Biodesign research · 2022Article
- Interactions of Globular and Ribbon [γ4E]GID with α4β2 Neuronal Nicotinic Acetylcholine Receptor.Marine drugs · 2021Article
- The Allosteric Activation of α7 nAChR by α-Conotoxin MrIC Is Modified by Mutations at the Vestibular Site.Toxins · 2021Article
- Potency- and Selectivity-Enhancing Mutations of Conotoxins for Nicotinic Acetylcholine Receptors Can Be Predicted Using Accurate Free-Energy Calculations.Marine drugs · 2021Article
- Virtual screening of peptides with high affinity for SARS-CoV-2 main protease.Computers in biology and medicine · 2021Article
- The new COST Action European Venom Network (EUVEN)-synergy and future perspectives of modern venomics.GigaScience · 2021Article
- Mass spectrometric identification andSaudi journal of biological sciences · 2021Article
- Novel Three-Finger Neurotoxins fromToxins · 2021Article
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Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
Abstract
Venom peptide toxins such as conotoxins play a critical role in the characterization of nicotinic acetylcholine receptor (nAChR) structure and function and have potential as nervous system therapeutics as well. However, the lack of solved structures of conotoxins bound to nAChRs and the large size of these peptides are barriers to their computational docking and design. We addressed these challenges in the context of the α4β2 nAChR, a widespread ligand-gated ion channel in the brain and a target for nicotine addiction therapy, and the 19-residue conotoxin α-GID that antagonizes it. We developed a docking algorithm, ToxDock, which used ensemble-docking and extensive conformational sampling to dock α-GID and its analogs to an α4β2 nAChR homology model. Experimental testing demonstrated that a virtual screen with ToxDock correctly identified three bioactive α-GID mutants (α-GID[A10V], α-GID[V13I], and α-GID[V13Y]) and one inactive variant (α-GID[A10Q]). Two mutants, α-GID[A10V] and α-GID[V13Y], had substantially reduced potency at the human α7 nAChR relative to α-GID, a desirable feature for α-GID analogs. The general usefulness of the docking algorithm was highlighted by redocking of peptide toxins to two ion channels and a binding protein in which the peptide toxins successfully reverted back to near-native crystallographic poses after being perturbed. Our results demonstrate that ToxDock can overcome two fundamental challenges of docking large toxin peptides to ion channel homology models, as exemplified by the α-GID:α4β2 nAChR complex, and is extendable to other toxin peptides and ion channels. ToxDock is freely available at rosie.rosettacommons.org/tox_dock.
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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 Socratic graph.