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Ukr. Bioorg. Acta 2020, Vol. 15, N1, 12-19.

In silico binding affinity studies of phenyl-substituted 1,3-oxazoles with protein molecules

Maryna Yu. Zhuravlova 1, Nataliya V. Obernikhina 2, Stepan G. Pilyo 3, Maryna V. Kachaeva 3, Oleksiy D. Kachkovsky 3, Volodymyr S. Brovarets 3

1National University of "Kyiv-Mohyla Academy", 2 Skovoroda St., Kyiv, 04070, Ukraine
2O. O. Bogomolets National Medical University, 13 Shevchenko Blvd., Kyiv, 01601, Ukraine
tel.: +380-96-225-7764; e-mail: nataliya.obernikhina@nmu.ua
3V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine

The new model approach of interaction between the pharmacophores with bio-molecules, fragment-to-fragment, is presented. It is a new step of the molecular modeling and takes correctly into consideration not only the spatial complementarity of the interacted molecules but also the contribution of the stacking π-π-electron interaction and hydrogen bonds. As an example, the correct analysis of the interaction of the biological active phenyl-substituted 1,3-oxazoles with protein fragments is performed. It was shown that the length and energy of the hydrogen bond uniquely depend on the chemical constitution of both components in the created complex [Pharmacophore(Oxazole)-Biomolecule (H-X)]. The binding energy regularly decreases in the series X
O, S, NH (fragments of the corresponding biomolecules). It should be pointed out that introduction of the conjugated phenyl groups at positions 2 and 5 of oxazoles increase the stability of the possibly generated complex Pharmacophore-Biomolecule [Pharm-BioM] with fragments of the corresponding biomolecules along the core of oxazole by 0.2 and 0.5 kcal/mole. At the same time, modeling of the possibly generated complex [Pharm-BioM] by phenyl substituents at position 2 and 5 of 1,3-oxazole with phenylalanine as a fragment of protein molecules additionally stabilizes complex by 2.5 kcal/mole by π-stacking mechanism. It seems, the observed biological activity of the phenyl substituted 1,3-oxazole is rather connected with the possibility to generate the stable complex due to the formation of additional bonds with other fragments (conjugated phenyl core). The calculations give that such substituents do not cause spatial hindrances with the polypeptide chain.

biological affinity, 1,3-oxazoles, quantum chemical calculations, [Pharm-BioM] complex, π-stacking interaction, hydrogen bonds.

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