Cited by 36Computational Drug Discovery MethodsAdvanced Chemical Physics StudiesEnzyme function and inhibition

Ranking power of the SQM/COSMO scoring function on carbonic anhydrase II-inhibitor complexes.

Pecina, Adam, Brynda, Jiří, Vrzal, Lukáš, Gnanasekaran, Ramachandran, Hořejší, Magdalena, Eyrilmez, Saltuk M., Řezáč, Jan, Lepšík, Martin +5 more·2018·ChemPhysChem

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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Crossref · 10.1002/cphc.201701104

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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).”

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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
Venue
ChemPhysChem
Publisher
Wiley
Published
2018-02-19
Volume
19
Issue
7
Pages
873-879
ISSN
  • 1439-4235 (ISSN-L)
  • 1439-7641
OpenAlex
W4240207195
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

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