Investigation of some potential drugs via density functional theory and quantum theory of atoms in molecules

Abstract

This research work has been carried out to understand the binding newlinemode of a few important drugs with human enzymes employing modern newlinetheoretical methods. newlineThe crystal structure of 2-acetamidophenyl acetate (2-AAPA) newlinecommonly used as influenza neuraminidase inhibitor has been solved newlineexperimentally and theoretically to analyze polymorphism. Molecular docking newlineand molecular dynamics have been performed for the 2-AAPA-neuraminidase newlinecomplex as the ester-derived benzoic group shows several biological newlineproperties. The X-ray diffraction studies confirmed that the 2-AAPA crystals newlineare stabilized by N H···O type of intermolecular interactions. Possible newlineconformers of 2-AAPA crystal structures were computationally predicted newlineby ab initio methods and the stable crystal structure was identified. Hirshfeld newlinesurface analysis of both experimental and predicted crystal structure exhibits newlinethe intermolecular interactions associated with 2D fingerprint plots. The newlinelowest docking score and intermolecular interactions of 2-AAPA molecule newlineagainst influenza neuraminidase confirm the binding affinity of the 2-AAPA newlinecrystals. The quantum theory of atoms in molecules analysis of these newlineintermolecular interactions was implemented to understand the charge density newlineredistribution of the molecule in the active site of influenza neuraminidase to newlinevalidate the strength of the interactions. newlineThe inhibition activity of the historical antiepileptic drug newlinephenobarbital (PB) on human cytochrome P450 2B6 (CYP2B6) has been newlineinvestigated by computational methods. Both hydrophobic and electrostatic newlineintermolecular interactions have been observed in docking analysis. newline