ReviewJournal of computer-aided molecular design2017
Overview of the SAMPL5 host-guest challenge: Are we doing better?
Review in Journal of computer-aided molecular design, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 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
- More protein-ligand data are needed for AlphaFold-like models to enable drug discovery.Current opinion in structural biology · 2026Review
- Binding Free Energies without Alchemy.ArXiv · 2026Article
- Committors without Descriptors.Journal of chemical theory and computation · 2026Article
- Blind Challenges Let Us See the Path Forward for Predictive Models.Journal of chemical information and modeling · 2026Article
- LamNet: an alchemical-path-aware graph neural network to accelerate binding free energy calculations for drug discovery and beyond.National science review · 2026Article
- Solvation Free Energies of Drug-like Molecules via Fast Growth in an Explicit Solvent: Assessment of the AM1-BCC, RESP/HF/6-31G*, RESP-QM/MM, and ABCG2 Fixed-Charge Approaches.Journal of chemical theory and computation · 2025Article
- Expanded ensemble predictions of toluene-water partition coefficients in the SAMPL9 logPhysical chemistry chemical physics : PCCP · 2025Article
- Rationalizing protein-ligand interactions via the effective fragment potential method and structural data from classical molecular dynamics.The Journal of chemical physics · 2025Article
- Multi-Objective Loss Function For Free Energy Calculations.ACM-BCB ... ... : the ... ACM Conference on Bioinformatics, Computational Biology and Biomedicine. ACM Conference on Bioinformatics, Computational Biology and Biomedicine · 2025Article
- Host-Guest Binding Free Energies à la Carte: An Automated OneOPES Protocol.Journal of chemical theory and computation · 2024Article
- Calculation of protein-ligand binding entropies using a rule-based molecular fingerprint.Biophysical journal · 2024Article
- The Open Force Field Initiative: Open Software and Open Science for Molecular Modeling.The journal of physical chemistry. B · 2024Article
- The SAMPL9 host-guest blind challenge: an overview of binding free energy predictive accuracy.Physical chemistry chemical physics : PCCP · 2024Article
- Tuning Potential Functions to Host-Guest Binding Data.Journal of chemical theory and computation · 2024Article
- Expanded ensemble predictions of absolute binding free energies in the SAMPL9 host-guest challenge.Physical chemistry chemical physics : PCCP · 2023Article
- An overview of the SAMPL8 host-guest binding challenge.Journal of computer-aided molecular design · 2022Article
- A Physics-Guided Neural Network for Predicting Protein-Ligand Binding Free Energy: From Host-Guest Systems to the PDBbind Database.Biomolecules · 2022Article
- CACHE (Critical Assessment of Computational Hit-finding Experiments): A public-private partnership benchmarking initiative to enable the development of computational methods for hit-finding.Nature reviews. Chemistry · 2022Article
- Obtaining QM/MM binding free energies in the SAMPL8 drugs of abuse challenge: indirect approaches.Journal of computer-aided molecular design · 2022Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The ability to computationally predict protein-small molecule binding affinities with high accuracy would accelerate drug discovery and reduce its cost by eliminating rounds of trial-and-error synthesis and experimental evaluation of candidate ligands. As academic and industrial groups work toward this capability, there is an ongoing need for datasets that can be used to rigorously test new computational methods. Although protein-ligand data are clearly important for this purpose, their size and complexity make it difficult to obtain well-converged results and to troubleshoot computational methods. Host-guest systems offer a valuable alternative class of test cases, as they exemplify noncovalent molecular recognition but are far smaller and simpler. As a consequence, host-guest systems have been part of the prior two rounds of SAMPL prediction exercises, and they also figure in the present SAMPL5 round. In addition to being blinded, and thus avoiding biases that may arise in retrospective studies, the SAMPL challenges have the merit of focusing multiple researchers on a common set of molecular systems, so that methods may be compared and ideas exchanged. The present paper provides an overview of the host-guest component of SAMPL5, which centers on three different hosts, two octa-acids and a glycoluril-based molecular clip, and two different sets of guest molecules, in aqueous solution. A range of methods were applied, including electronic structure calculations with implicit solvent models; methods that combine empirical force fields with implicit solvent models; and explicit solvent free energy simulations. The most reliable methods tend to fall in the latter class, consistent with results in prior SAMPL rounds, but the level of accuracy is still below that sought for reliable computer-aided drug design. Advances in force field accuracy, modeling of protonation equilibria, electronic structure methods, and solvent models, hold promise for future improvements.
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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.