Abstract

Alzheimer’s disease is one of the most fatal dementia occurring in elderly persons. LRP6 and DKK1 proteins are found in the senile plaques of Alzheimer’s disease patients. Inducing the disassociation/inhibition of the LRP6–DKK1 complex is a vital mechanism for the treatment of Alzheimer’s disease. This study accomplished its goal of targeting potent inhibitors against LRP6 by molecular modeling techniques such as high throughput virtual screening and molecular dynamics simulations. Zinc database compounds were docked in the hydrophobic patch of LRP6 and in the active site of DKK1 using the GLIDE module. The initial docking results were well exemplified to amino acid residues interacting on the hydrophobic patch of LRP6 and active sites of DKK1. Further, the best hit compounds (866) were again redocked with Glide XP and finally six lead compounds were identified as the best inhibitors against LRP6 which was later confirmed by molecular dynamics simulation studies.