ArticleThe journal of physical chemistry. B2021
Challenges Encountered Applying Equilibrium and Nonequilibrium Binding Free Energy Calculations.
Article in The journal of physical chemistry. B, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Fully Automatable Relative Binding Free Energy Calculations with Enhanced Sampling Using FAST/MBAR.Journal of chemical theory and computation · 2026Article
- Smoother Alchemical Transformations via Enveloping Distribution Sampling for Free-Energy Estimation.Journal of chemical theory and computation · 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
- Molecular determinants of arginine versus lysine cation-π interactions in biomolecular condensates.Communications chemistry · 2026Article
- An Automated Workflow for Diagnosing Sampling Issues Caused by Slow Torsional Motions in Molecular Simulations.Journal of chemical information and modeling · 2026Article
- Accelerating fragment-based drug discovery using grand canonical nonequilibrium candidate Monte Carlo.Nature communications · 2025Article
- Equilibrium and Nonequilibrium Ensemble Methods for Accurate, Precise and Reproducible Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2025Article
- Host-Guest Binding Free Energies à la Carte: An Automated OneOPES Protocol.Journal of chemical theory and computation · 2024Article
- Absolute Binding Free Energies with OneOPES.The journal of physical chemistry letters · 2024Article
- Automated Adaptive Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2024Article
- Impact of protein conformations on binding free energy calculations in the beta-secretase 1 system.Journal of computational chemistry · 2024Article
- Kartograf: A Geometrically Accurate Atom Mapper for Hybrid-Topology Relative Free Energy Calculations.Journal of chemical theory and computation · 2024Article
- PopShift: A Thermodynamically Sound Approach to Estimate Binding Free Energies by Accounting for Ligand-Induced Population Shifts from a Ligand-Free Markov State Model.Journal of chemical theory and computation · 2024Article
- Tuning Potential Functions to Host-Guest Binding Data.Journal of chemical theory and computation · 2024Article
- Fast free energy estimates from λ-dynamics with bias-updated Gibbs sampling.Nature communications · 2023Article
- Accelerating Alchemical Free Energy Prediction Using a Multistate Method: Application to Multiple Kinases.Journal of chemical information and modeling · 2023Article
- Identifying and Overcoming the Sampling Challenges in Relative Binding Free Energy Calculations of a Model Protein:Protein Complex.Journal of chemical theory and computation · 2023Article
- Identifying and overcoming the sampling challenges in relative binding free energy calculations of a model protein:protein complex.bioRxiv : the preprint server for biology · 2023Article
- Article
- Molecular Modelling of Ionic Liquids: Situations When Charge Scaling Seems Insufficient.Molecules (Basel, Switzerland) · 2023Article
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Authors and funding
4 authors.
Funding
Abstract
Binding free energy calculations have become increasingly valuable to drive decision making in drug discovery projects. However, among other issues, inadequate sampling can reduce accuracy, limiting the value of the technique. In this paper, we apply absolute binding free energy calculations to ligands binding to T4 lysozyme L99A and HSP90 using equilibrium and nonequilibrium approaches. We highlight sampling problems encountered in these systems, such as slow side chain rearrangements and slow changes of water placement upon ligand binding. These same types of challenges are also likely to show up in other protein-ligand systems, and we propose some strategies to diagnose and test for such problems in alchemical free energy calculations. We also explore similarities and differences in how the equilibrium and the nonequilibrium approaches handle these problems. Our results show the large amount of work still to be done to make free energy calculations robust and reliable and provide insight for future research in this area.
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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.