Halogen Bonds in Ligand-Protein Systems: Molecular Orbital Theory for Drug Design.,Journal of Chemical Information and Modeling

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Halogen Bonds in Ligand-Protein Systems: Molecular Orbital Theory for Drug Design.
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2020-01-31 , DOI: 10.1021/acs.jcim.9b00946
Enrico Margiotta _{1,

2} , Stephanie C C van der Lubbe ₁ , Lucas de Azevedo Santos _{1,

3} , Gabor Paragi _{1,

4,

5} , Stefano Moro ₂ , F Matthias Bickelhaupt _{1,

6} , Célia Fonseca Guerra _{1,

7}

Affiliation

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.

中文翻译：

配体-蛋白质系统中的卤素键：药物设计的分子轨道理论。

卤素键在药物化学中非常重要，因为药物的卤化通常会提高对蛋白质活性位点的选择性和功效。然而，由于缺乏对键合机理进行透彻的理论研究，而侧重于药物受体系统的实际复杂性，因此，对卤素键相互作用的准确建模仍然是一个挑战。我们对配体/肽样系统的系统量子化学研究表明，卤素键是由与氢键相同的键相互作用驱动的。除了静电和色散相互作用外，我们的键合分析基于定量的Kohn-Sham分子轨道理论以及能量分解分析，

更新日期：2020-01-31

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