ArticleCommunications chemistry2021
Accurate absolute free energies for ligand-protein binding based on non-equilibrium approaches.
Article in Communications chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Smoother Alchemical Transformations via Enveloping Distribution Sampling for Free-Energy Estimation.Journal of chemical theory and computation · 2026Article
- Large-Scale Collaborative Assessment of Binding Free Energy Calculations for Drug Discovery Using OpenFE.Journal of chemical information and modeling · 2026Article
- NEMAT: An Automated Nonequilibrium Free-Energy Framework for Predicting Ligand Affinity in Membrane Proteins.Journal of chemical information and modeling · 2026Article
- Molecular Modeling of the Pathogenetic Mechanisms of Neuropsychiatric Disorders.International journal of molecular sciences · 2026Review
- Efficient Binding Affinity Estimation for Fragment-Based Compounds Using a Separated Topologies Approach.Journal of chemical information and modeling · 2026Article
- Ensemble molecular dynamics for predicting binding energies of DNA intercalators.RSC advances · 2026Article
- Computing Solvation Free Energies of Small Molecules with Experimental Accuracy.Journal of the American Chemical Society · 2026Article
- Herbal medicine beyond probiotics: Yiyi Fuzi Baijiang powder and the holistic regulation of gut microbiota in ulcerative colitis.World journal of gastroenterology · 2026Article
- Ligand-Binding Free Energy Simulations of Membrane Proteins.Advances in experimental medicine and biology · 2026Review
- Assessment of the Binding Patterns for Endocrine Disrupting Chemicals in Complex with Estrogen and Androgen Receptors by Leveraging the Asclepios Enalos KNIME Nodes.Journal of chemical information and modeling · 2025Article
- Targeting RNA with small molecules using state-of-the-art methods provides highly predictive affinities of riboswitch inhibitors.Communications biology · 2025Article
- Advancing Binding Affinity Calculations: A Non-Equilibrium Simulations Approach for Calculation of Relative Binding Free Energies in Systems with Trapped Waters.Journal of chemical theory and computation · 2025Article
- Quantification of the Impact of Structure Quality on Predicted Binding Free Energy Accuracy.Journal of chemical information and modeling · 2025Article
- Estimation of Absolute Binding Free Energies for Drugs That Bind Multiple Proteins.Journal of chemical information and modeling · 2025Article
- Predicting Thermodynamic Stability at Protein G Sites with Deleterious Mutations Using λ-Dynamics with Competitive Screening.The journal of physical chemistry letters · 2025Article
- Nonequilibrium Binding Free Energy Simulations: Minimizing Dissipation.Journal of chemical theory and computation · 2025Article
- Large-scale energy decomposition for the analysis of protein stability.Cell stress & chaperones · 2025Article
- Article
- Equilibrium and Nonequilibrium Ensemble Methods for Accurate, Precise and Reproducible Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2025Article
- Navigating structure-based drug discovery with emerging innovations in physics- and knowledge-based approaches.npj drug discovery · 2025Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The accurate calculation of the binding free energy for arbitrary ligand-protein pairs is a considerable challenge in computer-aided drug discovery. Recently, it has been demonstrated that current state-of-the-art molecular dynamics (MD) based methods are capable of making highly accurate predictions. Conventional MD-based approaches rely on the first principles of statistical mechanics and assume equilibrium sampling of the phase space. In the current work we demonstrate that accurate absolute binding free energies (ABFE) can also be obtained via theoretically rigorous non-equilibrium approaches. Our investigation of ligands binding to bromodomains and T4 lysozyme reveals that both equilibrium and non-equilibrium approaches converge to the same results. The non-equilibrium approach achieves the same level of accuracy and convergence as an equilibrium free energy perturbation (FEP) method enhanced by Hamiltonian replica exchange. We also compare uni- and bi-directional non-equilibrium approaches and demonstrate that considering the work distributions from both forward and reverse directions provides substantial accuracy gains. In summary, non-equilibrium ABFE calculations are shown to yield reliable and well-converged estimates of protein-ligand binding affinity.
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Registered trials
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