Elucidation the Toxicity Mechanism of Zinc Oxide Nanoparticle Using Molecular Docking Approach With Proteins

Abstract

Objective: At present, toxicological tests are resource-intensive, time-consuming and require a large pool of animal models for toxicity assessment. To speed up the toxicity evaluation and to reduce animal suffering during toxicity assessment, the use of alternative methods including computational models is in high demand. The computational toxicity prediction methods are very helpful for the regulatory bodies to quickly assess the health impact of nanomaterial materials. In the present work, we have examined the mechanism of zinc oxide nanoparticle (ZnO-NP)-proteins interaction and their effect of surface chemistries of ZnO-NP on the bioactive conformation of chemokines and other cytological proteins using in silico molecular docking approaches.Methods: Molecular docking study was conducted using AutoDock 4.0 version and the visualization result using Discover Studio 4.0. Results:In the present study, we observed that ZnO-NP has high binding affinity with the mitogen-activated protein kinases (P-38), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) proteins, and matrix metallopeptidase-9 with docking energies −8.81, −7.64, and −7.27 Kcal/Mol, respectively, involving with hydrogen, metal acceptor, and electrostatic interaction. The top interacting amino acid residues with ZnO-NP are GLY, PHE, ARG, ASP, GLN, and ASN. Conclusion:Thus, based on the molecular docking studies, we determine that the ZnO-NP is strongly interacting with the chemokines and other cytological proteins thus responsible for blocking of the activation stimuli for these proteins to initiate the biological signals for the proper functioning. We have also extracted the information of interaction pattern of ZnO-NP with the surface-enriched amino acid residues of chemokine and cytological proteins using molecular docking approach.

Current Strategies in Assessment of Nanotoxicity: Alternatives to In Vivo Animal Testing

“…Thus far, computational modeling has utilized the protein crystal structure to investigate the cytotoxic effects and potential risks associated with functionalized NPs in many fields of nanotechnology [ 72 , 73 , 74 , 75 ]. For instance, cytochrome P450 (CYP) is an important enzyme system for drug metabolism.…”

Molecular Docking Approach for Biological Interaction of Green Synthesized Nanoparticles

“…P38 (PDB ID: 3W8Q) had the highest binding affinity (−8.81 kcal/mol), while IL-1B (PDB ID: 1I1B) had the lowest (−3.23 kcal/mol). Furthermore, ZnO NPs were studied as α-glucosidase enzyme inhibitors, a popular target for the management of diabetes [ 137 ]. When ZnO NPs were generated at the 500 °C calcination temperature, they had the strongest binding energy to this enzyme (−13.64 kcal/mol), with a size of around 32 nm [ 126 ].…”

UNLOCKING THE THERAPEUTIC POTENTIAL: EXPLORING NF-κB AS a VIABLE TARGET FOR DIVERSE PHARMACOLOGICAL APPROACHES

“…It was observed that ZnO-NP (zinc oxide nanoparticles) has a strong binding affinity with NF-κB, suggesting a potential interaction between these nanoparticles and the protein. This interaction may have implications for the regulation of inflammation and immune responses in the body [7].…”