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Discovering protein−ligand chalcogen bonding in the protein data bank using endocyclic sulfur-containing heterocycles as ligand search subsets

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Abstract

The chalcogen bond, the noncovalent, electrostatic attraction between covalently bonded atoms in group 16 and Lewis bases, is present in protein−ligand interactions based on X-ray structures deposited in the Protein Data Bank (PDB). Discovering protein−ligand chalcogen bonding in the PDB employed a strategy that focused on searching the database for protein complexes of five-membered, heterocyclic ligands containing endocyclic sulfur with endo electron-withdrawing groups (isothiazoles; thiazoles; 1,2,3-, 1,2.4-, 1,2,5-, 1,3,4-thiadiazoles) and thiophenes with exo electron-withdrawing groups, e.g., 2-chloro, 2-bromo, 2-amino, 2-alkylthio. Out of 930 ligands investigated, 33 or 3.5% have protein−ligand S---O interactions of which 31 are chalcogen bonds and two appear to be S---HO hydrogen bonds. The bond angles for some of the chalcogen bonds found in the PDB are less than 90°, and an electrostatic model is proposed to explain this phenomenon.

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Acknowledgments

The author thanks Dr. Jane S. Murray for providing the calculations and graphics in Figs. 1 and 11 and for helpful discussions.

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  1. American Institutes for Research, 1000 Thomas Jefferson St. NW, Washington, DC, 20007-3835, USA

    Miguel O. Mitchell

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Mitchell, M.O. Discovering protein−ligand chalcogen bonding in the protein data bank using endocyclic sulfur-containing heterocycles as ligand search subsets. J Mol Model 23, 287 (2017). https://doi.org/10.1007/s00894-017-3452-3

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