ArticleChemical science2019
Large scale relative protein ligand binding affinities using non-equilibrium alchemy.
Article in Chemical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed.
- One Blob to Rule Them All: A Universal Dual-Topology Nonequilibrium Framework for Relative and Absolute Binding Free Energies via a Lennard-Jones Blob Reference.Journal of chemical theory and computation · 2026Article
- Collective Variable-Guided Engineering of the Free-Energy Surface of a Small Peptide.Journal of chemical information and modeling · 2026Article
- Bridging between Structure-Based and Data-Driven Affinity Prediction.Journal of chemical information and modeling · 2026Article
- ModBindProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Emerging Insights into the Distinct Pharmacological Mechanisms of Buprenorphine.Journal of chemical information and modeling · 2026Article
- Large-Scale Collaborative Assessment of Binding Free Energy Calculations for Drug Discovery Using OpenFE.Journal of chemical information and modeling · 2026Article
- Molecular Dynamics Workflows to Compute Large-Scale Sets of Absolute Binding Free Energies Aiding Drug Candidate and Binding Pose Selection.Journal of chemical theory and computation · 2026Article
- NEMAT: An Automated Nonequilibrium Free-Energy Framework for Predicting Ligand Affinity in Membrane Proteins.Journal of chemical information and modeling · 2026Article
- The Last Mile Problem: A Critical Assessment of Physics-Based and AI Tools for Small Molecule Binding Prediction in Virtual Screening.Journal of chemical information and modeling · 2026Article
- Accelerated Combinatorial Drug Design for Human Immunodeficiency Virus Resistance through Seeded Multisite λ-Dynamics.Journal of chemical theory and computation · 2026Article
- Efficient Binding Affinity Estimation for Fragment-Based Compounds Using a Separated Topologies Approach.Journal of chemical information and modeling · 2026Article
- Doing More with Less: Accurate and Scalable Ligand Free Energy Calculations by Focusing on the Binding Site.Journal of chemical information and modeling · 2026Article
- The Open Molecular Software Foundation (OMSF) and the Growing Role of Open Source Software in Molecular Modeling.Journal of chemical information and modeling · 2026Review
- Molecular Design with Artificial Intelligence: Progress and Perspectives for Small Molecules.Chemical reviews · 2026Review
- Computing Solvation Free Energies of Small Molecules with Experimental Accuracy.Journal of the American Chemical Society · 2026Article
- Quantum mechanics in drug design: Progress, challenges, and future frontiers.Communicative & integrative biology · 2026Review
- In silico-driven protocol for hit-to-lead optimization: a case study on PDE9A inhibitors.Journal of computer-aided molecular design · 2025Article
- Article
- Evaluation of the ABCG2 Charge Model in Protein-Ligand Binding Free-Energy Calculations.Journal of chemical information and modeling · 2025Article
- 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
80 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ligand binding affinity calculations based on molecular dynamics (MD) simulations and non-physical (alchemical) thermodynamic cycles have shown great promise for structure-based drug design. However, their broad uptake and impact is held back by the notoriously complex setup of the calculations. Only a few tools other than the free energy perturbation approach by Schrödinger Inc. (referred to as FEP+) currently enable end-to-end application. Here, we present for the first time an approach based on the open-source software pmx that allows to easily set up and run alchemical calculations for diverse sets of small molecules using the GROMACS MD engine. The method relies on theoretically rigorous non-equilibrium thermodynamic integration (TI) foundations, and its flexibility allows calculations with multiple force fields. In this study, results from the Amber and Charmm force fields were combined to yield a consensus outcome performing on par with the commercial FEP+ approach. A large dataset of 482 perturbations from 13 different protein-ligand datasets led to an average unsigned error (AUE) of 3.64 ± 0.14 kJ mol
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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.