Insilico Designing and Development of Drug Inhibitor to PSEN 1 Protein in Alzheimer's disease

There are at least four well-confirmed genes responsible for Alzheimer's disease (AD), the most common form of dementia.In addition, many reports indicate an association between the disease and genetic variations in different gene candidates.Approximately 5-10% of patients develop an early age-at-onset AD (before 65 years).The disease in up to 50% of such cases is explained by mutations in one of three genes: APP, presenilin 1 (PS1), and presenilin 2 (PS2) .Pathological mutations in these genes PS1 on Chromosome 14q24.3 and PS2 Genes on Chromosome 1q31-q42 are responsible for an autosomal dominant trait and cause A-beta accumulation in the brain. [ However, the pathological consequence of some mutations detected in small AD families is uncertain and needs further investigation.Recently, we proposed to use a systematic algorithm to classify mutations in known AD genes as possibly, probably, or definitely pathogenic.Leads were identified based on several physiochemical properties and we created our library with those new molecules that were generated based on Lipinski's rule of five.We carried out high throughput screening and molecular docking on 65 molecules from scaffolds selected.Screening of molecules was based on the criterions such as, TOPKAT and ADMET properties.Among the ligands used, only three compounds were identified to have interaction within the targeted domain.To be more specific about our drug candidate we suggest noname 3 to be the most potent molecule in terms of physiochemical and docking properties.These results suggest that the identified compounds have the potential to inhibit PSEN-1 binding in Alzheimer.