QSAR application of natural therapeutics inhibitors against Alzheimer's disease through in-silico virtual-screening, docking-simulation, molecular dynamics, and pharmacokinetic prediction analysis

Alzheimer's disease (AD) is a brain disorder that is known to be one of the deadliest diseases affecting humanity, especially adults from the age of sixty (60) years and above. It mostly affects thinking ability, behaviour and social skills, eventually, AD causes the brain to shrink and brain cells to die. To curb the menace of this disease, virtual screening of potent, non-toxic hybrid natural therapeutic inhibitors was performed on some inhibitors of AD. We performed simulations on the screened compounds and predicted their druggability. A model with satisfactory statistical properties was developed in this study. The ligands underwent molecular docking, C-19 exhibited the highest docked score of −12.8 ​kcal mol-1 against the target, while the referenced compound (harmine) indicated the lowest docked score of −8.2 ​kcal mol-1. The docked complex was validated using molecular dynamic simulations. Trajectory plots of C-19 were obtained and found to be stable. C-19 was stable during the 100 ns intervals which implies that the compounds were better than the referenced compound. In addition, ADMET has demonstrated that these ligands have good pharmacokinetic properties. All the evaluations were more comprehensive and beneficial to researchers and the medical community as outstanding results were obtained.