Screening and Elucidation of Selected Natural Compounds for Anti- Alzheimer's Potential Targeting BACE-1 Enzyme: A Case Computational Study.

BACKGROUND The present study clarifies the molecular interactions of human BACE1 with novel natural ligands and also with the well-known ligand 2, 2, 4-trihydroxychalcone and Galangin for comparison. OBJECTIVE The study of enzyme- ligands interaction is interesting, thus description of ligands binding to the active site of target molecule could be beneficial for better understanding the mechanism of the ligand on the target molecule. METHODS Lipinski rule of five and docking study were performed between ligands and enzyme using 'Autodock4.2'. RESULTS It was found that hydrogen bond interactions play a significant role in the accurate positioning of ligands within the 'active site' of BACE1 to permit docking. Such information may aid to propose the BACE1 -inhibitors and is estimated to aid in the safe medical use of ligands. Selected ligands of BACE1 also inhibit the aggregated amyloid beta peptide. The aggregation of amyloid peptides Aβ1-42 may be responsible for AD. CONCLUSION Scope lies in the determination of the 3-dimensional structure of BACE1 and ligands complex by X-ray crystallography to certify the explained data. To validate the enzyme -ligands results, we considered 2, 2, 4-trihydroxychalconeas and Galangin as a positive control. Moreover, the current study verifies that ligands are more capable inhibitors of human BACE1 compared to positive control with reference to ΔG values.