Yevheniia Velihina, N. Obernikhina, S. Pilyo, M. Kachaeva, O. Kachkovsky, V. Brovarets
{"title":"含氮双环杂环结合亲和力的硅晶研究:片段对片段的方法","authors":"Yevheniia Velihina, N. Obernikhina, S. Pilyo, M. Kachaeva, O. Kachkovsky, V. Brovarets","doi":"10.15407/bioorganica2020.02.049","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":23445,"journal":{"name":"Ukr. Bioorg. Acta 2020, Vol. 15, N2","volume":"50 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"In silico study of binding affinity of nitrogenous bicyclic heterocycles: fragment-to-fragment approach\",\"authors\":\"Yevheniia Velihina, N. Obernikhina, S. Pilyo, M. Kachaeva, O. Kachkovsky, V. Brovarets\",\"doi\":\"10.15407/bioorganica2020.02.049\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":23445,\"journal\":{\"name\":\"Ukr. Bioorg. Acta 2020, Vol. 15, N2\",\"volume\":\"50 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-12-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ukr. Bioorg. Acta 2020, Vol. 15, N2\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.15407/bioorganica2020.02.049\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ukr. Bioorg. Acta 2020, Vol. 15, N2","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.15407/bioorganica2020.02.049","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.