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
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
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.