ArticleJournal of chemical theory and computation2024
What to Make of Zero: Resolving the Statistical Noise from Conformational Reorganization in Alchemical Binding Free Energy Estimates with Metadynamics Sampling.
Article in Journal of chemical theory and computation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- Dual-LAO for calculating fast and robust relative binding free energies of simple and complex transformations.Communications chemistry · 2026Article
- Toward Reconciling the Standard Binding Free Energy of Lenacapavir to HIV-1 Capsid with Experiment: Thermodynamic Effects of Solvent Buffer and Ligand Reorganization.The journal of physical chemistry. B · 2026Article
- Relative Binding Free Energy Estimation of Congeneric Ligands and Macromolecular Mutants with the Alchemical Transfer Method with Coordinate Swapping.Journal of chemical information and modeling · 2025Article
- Binding Selectivity Analysis from Alchemical Receptor Hopping and Swapping Free Energy Calculations.The journal of physical chemistry. B · 2024Article
- Adsorption of Flavonoids in a Transcriptional Regulator TtgR: Relative Binding Free Energies and Intermolecular Interactions.The journal of physical chemistry. B · 2024Article
- Alchemical Enhanced Sampling with Optimized Phase Space Overlap.Journal of chemical theory and computation · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
We introduce the self-relative binding free energy (self-RBFE) approach to evaluate the intrinsic statistical variance of dual-topology alchemical binding free energy estimators. The self-RBFE is the relative binding free energy between a ligand and a copy of the same ligand, and its true value is zero. Nevertheless, because the two copies of the ligand move independently, the self-RBFE value produced by a finite-length simulation fluctuates and can be used to measure the variance of the model. The results of this validation provide evidence that a significant fraction of the errors observed in benchmark studies reflect the statistical fluctuations of unconverged estimates rather than the models' accuracy. Furthermore, we find that ligand reorganization is a significant contributing factor to the statistical variance of binding free energy estimates and that metadynamics-accelerated conformational sampling of the torsional degrees of freedom of the ligand can drastically reduce the time to convergence.
Identifiers
What OpenQuestion holds
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.