ArticleJournal of chemical information and modeling2015
Is ring breaking feasible in relative binding free energy calculations?
Article in Journal of chemical information and modeling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed.
- Rational design of triazole tyrosinase inhibitors via integrated free energy calculations.Molecular diversity · 2026Article
- Dual-LAO for calculating fast and robust relative binding free energies of simple and complex transformations.Communications chemistry · 2026Article
- IMERGE-FEP: Improving Relative Free Energy Calculation Convergence with Chemical Intermediates.The journal of physical chemistry. B · 2025Article
- PairMap: An Intermediate Insertion Approach for Improving the Accuracy of Relative Free Energy Perturbation Calculations for Distant Compound Transformations.Journal of chemical information and modeling · 2025Article
- CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.The journal of physical chemistry. B · 2024Review
- Kartograf: A Geometrically Accurate Atom Mapper for Hybrid-Topology Relative Free Energy Calculations.Journal of chemical theory and computation · 2024Article
- Selection pressures on evolution of ribonuclease H explored with rigorous free-energy-based design.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Alchemical Free Energy Workflows for the Computation of Protein-Ligand Binding Affinities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- 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
- To Design Scalable Free Energy Perturbation Networks, Optimal Is Not Enough.Journal of chemical information and modeling · 2023Article
- TIES 2.0: A Dual-Topology Open Source Relative Binding Free Energy Builder with Web Portal.Journal of chemical information and modeling · 2023Article
- RestraintMaker: a graph-based approach to select distance restraints in free-energy calculations with dual topology.Journal of computer-aided molecular design · 2022Article
- Best practices for constructing, preparing, and evaluating protein-ligand binding affinity benchmarks [Article v0.1].Living journal of computational molecular science · 2022Article
- Dummy Atoms in Alchemical Free Energy Calculations.Journal of chemical theory and computation · 2021Article
- Scaffold Hopping Transformations Using Auxiliary Restraints for Calculating Accurate Relative Binding Free Energies.Journal of chemical theory and computation · 2021Article
- A strategy for proline and glycine mutations to proteins with alchemical free energy calculations.Journal of computational chemistry · 2021Article
- Drugging the undruggable: a computational chemist's view of KRASRSC medicinal chemistry · 2021Article
- TIES 20: Relative Binding Free Energy with a Flexible Superimposition Algorithm and Partial Ring Morphing.Journal of chemical theory and computation · 2021Article
- Free Energy Calculations for Protein-Ligand Binding Prediction.Methods in molecular biology (Clifton, N.J.) · 2021Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Our interest is relative binding free energy (RBFE) calculations based on molecular simulations. These are promising tools for lead optimization in drug discovery, computing changes in binding free energy due to modifications of a lead compound. However, in the "alchemical" framework for RBFE calculations, some types of mutations have the potential to introduce error into the computed binding free energies. Here we explore the magnitude of this error in several different model binding calculations. We find that some of the calculations involving ring breaking have significant errors, and these errors are especially large in bridged ring systems. Since the error is a function of ligand strain, which is unpredictable in advance, we believe that ring breaking should be avoided when possible.
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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.