In-silico docking and virtual screening of natural products as possible BACE1 inhibitors: a new hope for treatment of Alzheimer’s disease?

The most common cause of dementia and the fifth most prevalent cause of mortality in people over 65 is Alzheimer’s disease (Wung, 2020). A di↵erent pharmacological target for treating AD is needed due to the ongoing failure of present therapies. BACE1 is a widely recognized prospective therapeutic target for Alzheimer’s disease because it catalyzes the rate-determining step in the production of A peptides (Kumar et al., 2020). COCONUT database (Collection of Open Natural Products database) was screened for creating a library of natural products with the following filters: 1. molecular weight between 400-600 2. Lipinski’s role of five. One hundred best hits were downloaded as a library. We used the protein 3D structure of BACE1 (PDB ID: 7MYI; X-Ray; Chain A/B; 1.25 ˚A) for docking. All the ligands and the 3D structure of the BACE1 were then prepared using the Schro¨dinger suite (Maestro 11.5) Ligprep module and ProPrep wizard, respectively. Ligand docking in the module GLIDE of the Schro¨dinger suite was used for the evaluation of the interaction between ligands and chain A of the target protein (opls2005 forcefield). Best ligands according to glide E-model and docking score were evaluated for pharmacokinetic properties predictions by Swiss ADMET, pkCSM, and ADMETlab 2.0. Molecular docking analyses of our natural products library found promising ligands that had excellent protein-ligand interactions with BACE1 and reasonable docking scores (CNP0278652, CNP0014230, CNP0385754, CNP0194616, CNP0178972, CNP0251096, CNP0393956 and CNP0366016). Some of these ligands displayed acceptable pharmacokinetic and physicochemical characteristics, such as good absorption, distribution, metabolism, and excretion (ADMET). BACE1 appears to be a promising target for the development of novel medications. Future in-vivo and in-vitro research is necessary to provide additional information about this target, nevertheless.

کلیدواژه های In-silico docking and virtual screening of natural products as possible BACE1 inhibitors: a new hope for treatment of Alzheimer’s disease?:

Alzheimer ، In-Silico ، Drug design ، Natural Products