Disruption of DYRK1A-induced hyperphosphorylation of amyloid-beta and tau protein in Alzheimer's disease: An integrative molecular modeling approach.

ABSTRACT: Alzheimer's disease (AD) is a neurological disorder caused by the abnormal accumulation of hyperphosphorylated proteins. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a dual phosphorylation enzyme which phosphorylates the amyloid-β (Aβ) and neurofibrillary tangles (NFTs). A high throughput virtual screening approach was applied to screen a library of 98,071 compounds against DYRK1A using different programs including AutoDock Vina, Smina, and idock. Based on the binding affinities, we selected 330 compounds for absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. Various pharmacokinetics parameters were predicted using the admetSAR server, and based on the pharmacokinetics results, 14 compounds were selected for cross-docking analysis u

SUBMITTER: Shukla R 

PROVIDER: S-EPMC9892649 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature