Screening, Docking, and Molecular Dynamics Study of Natural Compounds as an Anti-HER2 for the Management of Breast Cancer

Breast cancer (BC) is one of the most frequent types of cancer that affect women. Human epidermal growth factor receptor-2 (HER2) is responsible for 20% of all BC cases. The use of anti-HER2 natural compounds in the cure of BC that is HER2-positive patients has resulted in significant increases in survival in both early and advanced stages. The findings of in-silico research support the use of ligands as possible HER2 inhibitors, and molecules with high free energy of binding may have considerable anti-BC action, making them candidates for future drug development. The inhibitory activity of selected ligands like ZINC43069427 and ZINC95918662 against HER2 was found to be −11.0 and −8.50 kcal/mol, respectively. The amino acid residues Leu726, Val734, Ala751, Lys753, Thr798, Gly804, Arg849, Leu852, Thr862, and Asp863 were found in common interaction as compared to the control compound Lapatinib. Molecular dynamics study calculations of these selected potent inhibitors were conducted and found to be stable over the 50 ns simulation time in terms of root mean square deviation (RMSD), root-mean square fluctuation (RMSF), radius of gyration (Rg), and solvent accessible surface area (SASA). In addition, there are several parameters such as absorption, distribution, metabolism, and excretion toxicity (ADMET), physicochemical, and drug-likeness that were checked and found in good range to be potential lead-like molecules. Several drug-likeness rules like Lipinski, Ghose, Veber, Egan, and Muegge were checked and found to be positive for these rules. Based on these calculations and different parameters, these top two selected natural compounds can be used as potential candidates for anti-HER2 for the management of BC.