Halogen Bonds in Ligand-Protein Systems: Molecular Orbital Theory for Drug Design
| Autor: | F. Matthias Bickelhaupt, Célia Fonseca Guerra, Stephanie C. C. van der Lubbe, Enrico Margiotta, Stefano Moro, Gábor Paragi, Lucas de Azevedo Santos |
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| Přispěvatelé: | Theoretical Chemistry, AIMMS, Chemistry and Pharmaceutical Sciences |
| Rok vydání: | 2020 |
| Předmět: |
inorganic chemicals
General Chemical Engineering Library and Information Sciences Ligands 01 natural sciences Article Halogens Atomic orbital Computational chemistry 0103 physical sciences Theoretical Chemistry Halogen bond 010304 chemical physics Hydrogen bond Chemistry Ligand Halogenation Proteins Molecular orbital theory Hydrogen Bonding General Chemistry 0104 chemical sciences Computer Science Applications 010404 medicinal & biomolecular chemistry Drug Design Halogen Selectivity |
| Zdroj: | Journal of Chemical Information and Modeling Journal of Chemical Information and Modeling, 60, 1317-1328 Journal of chemical information and modeling, 60(3), 1317-1328. American Chemical Society Journal of Chemical Information and Modeling, 60, 3, pp. 1317-1328 Margiotta, E, van der Lubbe, S C C, de Azevedo Santos, L, Paragi, G, Moro, S, Bickelhaupt, F M & Fonseca Guerra, C 2020, ' Halogen Bonds in Ligand-Protein Systems : Molecular Orbital Theory for Drug Design ', Journal of chemical information and modeling, vol. 60, no. 3, pp. 1317-1328 . https://doi.org/10.1021/acs.jcim.9b00946 |
| ISSN: | 1549-960X 1549-9596 |
| DOI: | 10.1021/acs.jcim.9b00946 |
| Popis: | Halogen bonds are highly important in medicinal chemistry as halogenation of drugs, generally, improves both selectivity and efficacy toward protein active sites. However, accurate modeling of halogen bond interactions remains a challenge, since a thorough theoretical investigation of the bonding mechanism, focusing on the realistic complexity of drug-receptor systems, is lacking. Our systematic quantum-chemical study on ligand/peptide-like systems reveals that halogen bonding is driven by the same bonding interactions as hydrogen bonding. Besides the electrostatic and the dispersion interactions, our bonding analyses, based on quantitative Kohn-Sham molecular orbital theory together with energy decomposition analysis, reveal that donor-acceptor interactions and steric repulsion between the occupied orbitals of the halogenated ligand and the protein need to be considered more carefully within the drug design process. |
| Databáze: | OpenAIRE |
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