A Model of Interaction Between Apocynin and NADPH Oxidase Enzyme to Analyze the Possible Targets Responsible for Inhibition by Computational Analysis

Background/Aims: A multi-component enzyme system called NADPH oxidase (NOX) helps innate immunity by generating reactive oxygen species (ROS). NOX hyperactivation has been associated w several diseases. This enzyme is a membrane-bound complex made up of six subunits when it is active. These enzymatic subunits are considered to be potent inhibitors of enzyme activity and good targets for reducing oxidative stress. Methods: The present study aimed to analyze the possible targets: the different subunits of NOX, for their interactions with apocynin to identify its possible mechanism of inhibition for NOX, using in silico tools. Monomer, dimer, and trimer of apocynin were docked to various subunits of NOX. Results: Comparable glide scores were obtained when the monomer and dimer of apocynin were docked with p47phox complete subunit of NOX and were better than in comparison to trimer. Free Energy of Binding (FEB) was highest in the case of the trimer (-37.4 Kcal/mol), followed by the dimer (-21.2 Kcal/mol) and monomer (-18.2 Kcal/mol). Dimer obtained the highest glide score of 8.25 (FEB =-25.1 Kcal/mol) with p67phox-isoform 2. The PH domain of p47phox and the SH3 domain of p67phox have their own best binding energy with dimmer. While molecular docking with Rac-Zn-GD, P, dimer, and trimer have shown comparable FEB. The residues, on which the ligands were found to interact, were of major significance being present in those domains that vicinity to inhibit or activate the complex and are important for the protein structure and functioning. MDS studies have confirmed the findings that the Apocynin trimer molecule has superior stability and interactions with the enzyme complex. Conclusion: It can be concluded from the study that trimer and dimer have better interactions in terms of FEB with p67phox and p47phox, indicating the reported findings in the literature.