GV971 derived from marine acidic oligosaccharides has been used to cure Alzheimer's disease (AD). However, the molecular mechanism of its inhibition of the conformational transition of amyloid β-proteins (Aβ) is still unclear. Herein, molecular dynamics simulations were used to explore the molecular mechanism of the main GV971 components including DiM, TetraM, HexaM, and OctaM to inhibit the conformational conversion of the Aβ42 monomer. It is found that the GV971 components inhibit the conformational transition from α-helix to β-sheet and the hydrophobic collapse of the Aβ42 monomer. In addition, the binding energy analysis implies that both electrostatic and van der Waals interactions are beneficial to the binding of GV971 components to the Aβ42 monomer. Among them, electrostatic interactions occupy the dominant position. Moreover, the GV971 components mainly interact directly with the charged residues D1, R5, K16, and K28 by forming salt bridges and hydrogen bonds, which specifically bind to the N-terminal region of Aβ42.
Keywords: Alzheimer’s disease; GV971; carbohydrate; inhibitor; molecular dynamics simulations.