In-silico approaches in designing new drug candidates (THICAPA and POET) for alzheimer’s disease

Background: Memory and cognitive regression are the first symptoms of Alzheimer’s Disease (AD), which may progress to speech and mobility challenges which affecting around 35% of those who over the age of 80 years old. Preliminary study shows THICAPA and Palm Oil Extracted Tocotrienol (POET) is effective in reducing AD symptoms in Dorosophila melagnoster. Objective: The purpose of this study is to elucidate the binding interaction between THICAPA and POET towards APP and PS1 at the molecular level. Method: The binding of THICAPA and POET towards APP (PDB ID: 6SZF), PS1 (PDB ID: 7D8X), and their genetic mutation variations (APP variant n = 6, PS1 variant n = 200) have been studied using in-sillico molecular docking (Autodock 4.2) approaches and comparing the Binding Free Energy (BFE) of the binding interactions. Result: From the 416 dockings (n = 100 per docking, ∑n = 41,600), we revealed that all dockings had negative BFE which showed the low BFE towards both APP (E22K variant ΔG THICAPA = -6.20 kcal/mol, D23N variant ΔG POET = -7.25 kcal/mol) and PS1 (A413V variant ΔG THICAPA = -8.34 kcal/mol, L174M variant ΔG POET = -10.94 kcal/mol). Conclusion: THICAPA and POET showed a negative BFE with APP and PS1. Thus, the result suggesting that THICAPA and POET may be the potential drug candidates for treating AD.