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Persistent Identifier
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perma:LIST.P0EJTZ |
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Publication Date
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2026-07-06 |
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Title
| Extending quantum-mechanical benchmark accuracy to biological ligand-pocket interactions [* Cross-Reference *] |
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Other Identifier
| https://doi.org/10.1038/s41467-025-63587-9
OpenAlex ID: https://openalex.org/W4414601265 |
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Author
| Mirela Puleva (University of Luxembourg, Luxembourg Institute of Science and Technology, Luxembourg Institute of Socio-Economic Research) - ORCID: https://orcid.org/0000-0001-9853-6775
Leonardo Medrano Sandonas (University of Luxembourg, Max Bergmann Zentrum für Biomaterialien) - ORCID: https://orcid.org/0000-0002-7673-3142
Balázs D. Lőrincz (Budapest University of Technology and Economics, Montavid Thermodynamic Research Group) - ORCID: https://orcid.org/0000-0002-7573-8099
Jorge Charry (University of Luxembourg, Luxembourg Institute of Socio-Economic Research, Arbed (Luxembourg)) - ORCID: https://orcid.org/0000-0003-3069-2522
David Rogers (Oak Ridge National Laboratory) - ORCID: https://orcid.org/0000-0002-5187-1768
Péter R. Nagy (Budapest University of Technology and Economics, Pázmány Péter Catholic University, Montavid Thermodynamic Research Group) - ORCID: https://orcid.org/0000-0001-6692-0879
Alexandre Tkatchenko (University of Luxembourg, Luxembourg Institute of Science and Technology, Luxembourg Institute of Socio-Economic Research) - ORCID: https://orcid.org/0000-0002-1012-4854 |
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Point of Contact
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Use email button above to contact.
LIST QDKM (LIST) |
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Description
| Predicting the binding affinity of ligands to protein pockets is key in the drug design pipeline. The flexibility of ligand-pocket motifs arises from a range of attractive and repulsive electronic interactions during binding. Accurately accounting for all interactions requires robust quantum-mechanical (QM) benchmarks, which are scarce for ligand-pocket systems. Additionally, disagreement between “gold standard” Coupled Cluster (CC) and Quantum Monte Carlo (QMC) methods casts doubt on many benchmarks for larger non-covalent systems. We introduce the “QUantum Interacting Dimer” (QUID) benchmark framework containing 170 non-covalent (non-)equilibrium systems modeling chemically and structurally diverse ligand-pocket motifs. Symmetry-adapted perturbation theory shows that QUID broadly covers non-covalent binding motifs and energetic contributions. Robust binding energies are obtained using complementary CC and QMC methods, achieving agreement of 0.5 kcal/mol. The benchmark data analysis reveals that several dispersion-inclusive density functional approximations provide accurate energy predictions, though their atomic van der Waals forces differ in magnitude and orientation. Contrarily, semiempirical methods and empirical force fields require improvements in capturing non-covalent interactions (NCIs) for out-of-equilibrium geometries. The wide span of NCIs, highly accurate interaction energies, and analysis of molecular properties take QUID beyond the “gold standard” for QM benchmarks of ligand-protein systems. (2025-09-29)
***This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1038/s41467-025-63587-9 for the original and latest version of the publication*** (2026-07-01) |
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Subject
| Astronomy and Astrophysics; Chemistry; Computer and Information Science; Medicine, Health and Life Sciences; Physics |
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Keyword
| van der Waals force
Benchmark (surveying)
Flexibility (engineering)
Monte Carlo method
Range (aeronautics)
Quantum Monte Carlo
Density functional theory
Perturbation theory (quantum mechanics) |
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Topic Classification
| Advanced Chemical Physics Studies
Protein Structure and Dynamics
Computational Drug Discovery Methods |
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Deposit Date
| 2025-09-29 |
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Data Type
| Article |
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Data Source
| Nature Communications |
