ArticleNature chemistry2017
Dynamic undocking and the quasi-bound state as tools for drug discovery.
Article in Nature chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- AI accelerate the identification of druggable targets by 3D structures of proteins and compounds.NPJ precision oncology · 2026Review
- The covalent docking software landscape: features and applications in drug design.Briefings in bioinformatics · 2025Review
- Discovering Uncharted Binding Pockets on E3 Ligases Leads to the Identification of FBW7 Allosteric Modulators.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A bottom-up approach to find lead compounds in expansive chemical spaces.Communications chemistry · 2025Article
- The Quasi-Bound State as a Predictor of Relative Binding Free Energy.Journal of chemical information and modeling · 2025Article
- Mining Druggable Sites in Influenza A Hemagglutinin: Binding of the Pinanamine-Based Inhibitor M090.ACS medicinal chemistry letters · 2025Article
- Identification and Validation of New DNA-PKcs Inhibitors through High-Throughput Virtual Screening and Experimental Verification.International journal of molecular sciences · 2024Article
- SQM2.20: Semiempirical quantum-mechanical scoring function yields DFT-quality protein-ligand binding affinity predictions in minutes.Nature communications · 2024Article
- Drug Design in the Exascale Era: A Perspective from Massively Parallel QM/MM Simulations.Journal of chemical information and modeling · 2023Review
- DeepBindGCN: Integrating Molecular Vector Representation with Graph Convolutional Neural Networks for Protein-Ligand Interaction Prediction.Molecules (Basel, Switzerland) · 2023Article
- Lenalidomide Stabilizes Protein-Protein Complexes by Turning Labile Intermolecular H-Bonds into Robust Interactions.Journal of medicinal chemistry · 2023Article
- Open Binding Pose Metadynamics: An Effective Approach for the Ranking of Protein-Ligand Binding Poses.Journal of chemical information and modeling · 2022Article
- Cosolvent Sites-Based Discovery ofJournal of medicinal chemistry · 2022Article
- Development of an Automatic Pipeline for Participation in the CELPP Challenge.International journal of molecular sciences · 2022Article
- Computational Design of Inhibitors Targeting the Catalytic β Subunit ofAntibiotics (Basel, Switzerland) · 2022Article
- SAMPL7 protein-ligand challenge: A community-wide evaluation of computational methods against fragment screening and pose-prediction.Journal of computer-aided molecular design · 2022Article
- Discovery and In Vivo Proof of Concept of a Highly Potent Dual Inhibitor of Soluble Epoxide Hydrolase and Acetylcholinesterase for the Treatment of Alzheimer's Disease.Journal of medicinal chemistry · 2022Article
- PlayMolecule Glimpse: Understanding Protein-Ligand Property Predictions with Interpretable Neural Networks.Journal of chemical information and modeling · 2022Article
- Fragment Hotspot Mapping to Identify Selectivity-Determining Regions between Related Proteins.Journal of chemical information and modeling · 2022Article
- An Efficient Modern Strategy to Screen Drug Candidates Targeting RdRp of SARS-CoV-2 With Potentially High Selectivity and Specificity.Frontiers in chemistry · 2022Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is a pressing need for new technologies that improve the efficacy and efficiency of drug discovery. Structure-based methods have contributed towards this goal but they focus on predicting the binding affinity of protein-ligand complexes, which is notoriously difficult. We adopt an alternative approach that evaluates structural, rather than thermodynamic, stability. As bioactive molecules present a static binding mode, we devised dynamic undocking (DUck), a fast computational method to calculate the work necessary to reach a quasi-bound state at which the ligand has just broken the most important native contact with the receptor. This non-equilibrium property is surprisingly effective in virtual screening because true ligands form more-resilient interactions than decoys. Notably, DUck is orthogonal to docking and other 'thermodynamic' methods. We demonstrate the potential of the docking-undocking combination in a fragment screening against the molecular chaperone and oncology target Hsp90, for which we obtain novel chemotypes and a hit rate that approaches 40%.
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