Ranking power of the SQM/COSMO scoring function on carbonic anhydrase II-inhibitor complexes.
Abstract
Accurate prediction of protein–ligand binding affinities is essential for hit‐to‐lead optimization and virtual screening. The reliability of scoring functions can be improved by including quantum effects. Here, we demonstrate the ranking power of the semiempirical quantum mechanics (SQM)/implicit solvent (COSMO) scoring function by using a challenging set of 10 inhibitors binding to carbonic anhydrase II through Zn 2+ in the active site. This new dataset consists of the high‐resolution (1.1–1.4 Å) crystal structures and experimentally determined inhibitory constant (Ki) values. It allows for evaluation of the common approximations, such as representing the solvent implicitly or by using a single target conformation combined with a set of ligand docking poses. SQM/COSMO attained a good correlation of R2 of 0.56–0.77 with the experimental inhibitory activities, benefiting from careful handling of both noncovalent interactions (e.g. charge transfer) and solvation. This proof‐of‐concept study of SQM/COSMO ranking for metalloprotein–ligand systems demonstrates its potential for hit‐to‐lead applications.
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Results obtained using QM or hybrid QM/MM-based methods are very encouraging compared to standard scoring functions, principally when dealing with metalloproteins.
“The results obtained using QM or hybrid QM/MM-based methods are very encouraging when compared to the standard scoring functions, principally when dealing with metalloproteins (Chaskar et al., 2017; Pecina et al., 2018).”
From Empirical scoring functions for structure-based virtual screening: applications, critical aspects, and challenges (2018) · cites this paper as Pecina et al., 2018
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- Authors
- Pecina, A., Brynda, J., Vrzal, L., Gnanasekaran, R., Hořejší, M., Eyrilmez, S. M., Řezáč, J., Lepšík, M., Řezáčová, P., Hobza, P., Majer, P., Veverka, V., & Fanfrlík, J.
- Affiliations
- Czech Academy of Sciences (CZ)
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo nam. 2 16610 Prague 6 Czech Republic
- Pondicherry University (IN)
- Institute of Molecular Genetics of Czech Academy of Sciences Videnska 1083 14220 Prague 4 Czech Republic
- Corresponding author
- Veverka, Václav
- Fanfrlík, Jindřich
- ORCID
- Venue
- ChemPhysChem
- Publisher
- Wiley
- Published
- 2018-02-19
- Volume
- 19
- Issue
- 7
- Pages
- 873-879
- ISSN
- 1439-4235 (ISSN-L)
- 1439-7641
- OpenAlex
- W4240207195
- Semantic Scholar
- 9c79c58a40ca740180021446d16bca0feae606e0
- Cited by
- 36
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 8 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 3
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ChemPhysChem (publishedVersion)
- Funders
- Grantová Agentura České Republiky (P208/16-11321Y, GA15-05677S)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Chemical Physics Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Keywords
- carbonic anhydrase II, protein-ligand binding affinity prediction, implicit solvent, crystal structure, hit-to-lead optimization, virtual screening, charge transfer
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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