Program

P.29 -- Poster, IWTCP-3

Date: Wednesday, 29 July 2015

Time: 08h30 - 10h00

Analysis of Binding Affinity of Derivatives of Vitamin K3 to Fibrils of A$\beta$ peptides

Vu Thi Mui (1), Pham Dinh Quoc Huy (1,2) and Mai Suan Li (1,2)

(1) Institute for Computational Sciences and Technology, Ho Chi Minh City, Vietnam; (2) Institute of Physics, Polish Academy of Sciences, Warsaw, Poland

Aggregation of amyloid-beta (Aβ) has been proposed as the main cause of Alzheimer's disease (AD). Vitamin K deficiency has been linked to the pathogenesis of AD. Therefore, 4 vitamin K3 (VK3) analogues were proposed and studied for their anti-amyloidogenic activity. Chemical formulas for VK3-1, VK3-2, VK3-3 and VK3-4 are C14H14O6S, C14H12O7S, C17H12O6S, and C17H12O7S, respectively. Using docking method and all-atom (Gromos 96 43a1 force field) molecular dynamics simulations in explicit water, we studied their binding affinity to Aβ peptides and fibrils. The binding free energy was analyzed by the molecular mechanic-Poisson−Boltzmann surface area method (MM/PBSA). The results show that the electrostatic interaction correlates to the binding free energy better than the van der Waals interaction does. According to our estimations of the binding free energy the rank-ordering of binding affinity to Aβ is VK3-1 > VK3-3 > VK3-4 > VK3-2 implying that VK3-1 is the most prominent in preventing aggregation. However, we recommend VK3-3 for further in vitro and in vivo study as it can cross the blood brain barrier better than other compounds.

Presenter: Vu Thi Mui