ArticleProceedings of the National Academy of Sciences of the United States of America2013
Funnel metadynamics as accurate binding free-energy method.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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Who cites it
158 citing papers in PubMed.
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- Metadynamics Simulations Meet Ligand Design for the Reversible Inhibition of Human Peroxiredoxin 5.ACS omega · 2026Article
- Targeting the intrinsically disordered AR-NTD through a machine learning-based enhanced sampling workflow.Nature communications · 2026Article
- Article
- Resolving the ambiguous binding site of quercetin at the calcineurin subunit junction using funnel metadynamics with deep learning collective variables.Journal of computer-aided molecular design · 2026Article
- Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.Journal of chemical information and modeling · 2026Article
- Protonation-dependent substrate release in a bacterial homolog of vesicular glutamate.Biophysical journal · 2026Article
- Structural mechanisms underlying distinct binding and activities of 18:0 and 18:1 lysophosphatidic acids at LPA1 receptor.PLoS computational biology · 2026Article
- Revealing the Binding Mechanism of Gossypol on Bcl‑2 via Funnel Metadynamics Simulations.ACS omega · 2026Article
- Molecular Origins of Simultaneous Chemo-, Enantio-, and Substrate Selectivity in Non-Natural Photoenzymatic Radical Reactions.Journal of the American Chemical Society · 2025Article
- A Review of Global Optimization Methods for Molecular Structures: Algorithms, Applications and Perspectives.Journal of computational chemistry · 2025Review
- Structural basis for ligand promiscuity and high signaling activity of Kaposi's Sarcoma-associated Herpesvirus-encoded GPCR.Nature communications · 2025Article
- Article
- A direct computational assessment of vinculin-actin unbinding kinetics reveals catch-bonding behavior.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural Determinants of Buprenorphine Partial Agonism at the μ-Opioid Receptor.Journal of chemical information and modeling · 2025Article
- PDBrestore: A Free Web Interface for Processing and Fixing Protein Chains From Raw PDB Files.Journal of computational chemistry · 2025Article
- Unraveling the Molecular Basis for G-Quadruplex-Binders to ALS/FTD-Associated G4C2 Repeats of the C9orf72 Gene.Chembiochem : a European journal of chemical biology · 2025Article
- Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints.Journal of chemical theory and computation · 2025Article
- Pathway Specific Unbinding Free Energy Profiles of Ritonavir Dissociation from HIV-1 Protease.Biochemistry · 2025Article
98 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
Abstract
A detailed description of the events ruling ligand/protein interaction and an accurate estimation of the drug affinity to its target is of great help in speeding drug discovery strategies. We have developed a metadynamics-based approach, named funnel metadynamics, that allows the ligand to enhance the sampling of the target binding sites and its solvated states. This method leads to an efficient characterization of the binding free-energy surface and an accurate calculation of the absolute protein-ligand binding free energy. We illustrate our protocol in two systems, benzamidine/trypsin and SC-558/cyclooxygenase 2. In both cases, the X-ray conformation has been found as the lowest free-energy pose, and the computed protein-ligand binding free energy in good agreement with experiments. Furthermore, funnel metadynamics unveils important information about the binding process, such as the presence of alternative binding modes and the role of waters. The results achieved at an affordable computational cost make funnel metadynamics a valuable method for drug discovery and for dealing with a variety of problems in chemistry, physics, and material science.
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