含氮双环杂环结合亲和力的硅晶研究:片段对片段的方法

Yevheniia Velihina, N. Obernikhina, S. Pilyo, M. Kachaeva, O. Kachkovsky, V. Brovarets
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引用次数: 1

摘要

本文研究了模型芳香族氨基酸与杂环及其与吡啶缩合的衍生物的结合亲和性,并在片段对片段的方法框架下进行了描述。该模型描述了药物载体与生物分子之间的相互作用。仔细的数据分析表明,杂环叠加对π-电子体系的扩展导致了高能级的上移,而新的配位氮原子的出现伴随着供体-受体性质的降低。密度泛函理论(DFT) wB97XD/6-31(d,p)/对π-叠作用形成的杂环1-3与芳香氨基酸模型片段的π-配合物的计算表明,在苯丙氨酸向色氨酸转移过程中,π-配合物的稳定能增加。通过氢键机制对具有模型质子给体氨基酸的药效团配合物(H-B配合物)进行DFT计算表明,稳定能(DE)从单杂环到其缩合衍生物增加。如先前报道的[18],通过在恶唑循环中引入苯基自由基来扩展π-电子系统,导致[pharma - biom]配合物的稳定能量比通过吡啶循环合成的恶唑降低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In silico study of binding affinity of nitrogenous bicyclic heterocycles: fragment-to-fragment approach
The binding affinity of model aromatic amino acids and heterocycles and their derivatives condensed with pyridine were investigated in silico and are presented in the framework of fragment-to-fragment approach. The presented model describes interaction between pharmacophores and biomolecules. Scrupulous data analysis shows that expansion of the π-electron system by heterocycles annelation causes the shifting up of high energy levels, while the appearance of new the dicoordinated nitrogen atom is accompanied by decreasing of the donor-acceptor properties. Density Functional Theory (DFT) wB97XD/6-31(d,p)/calculations of π-complexes of the heterocycles 1-3 with model fragments of aromatic amino acids, which were formed by π-stack interaction, show an increase in the stabilization energy of π-complexes during the moving from phenylalanine to tryptophan. DFT calculation of pharmacophore complexes with model proton-donor amino acid by the hydrogen bonding mechanism (H-B complex) shows that stabilization energy (DE) increases from monoheterocycles to their condensed derivatives. The expansion of the π-electron system by introducing phenyl radicals to the oxazole cycle as reported earlier [18] leads to a decrease in the stabilization energy of the [Pharm-BioM] complexes in comparison with the annelated oxazole by the pyridine cycle.
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