Program

O.7 -- Oral, NCTP-42

Date: Monday, 31 July 2017

Time: 14h40 - 15h00

Replica Exchange Molecular Dynamics Study of the Truncated Amyloid Beta (11-40) Trimer in Solution

Son Tung Ngo (1,2,*), Huynh Minh Hung (3), Duc Toan Truong (4) and Minh Tho Nguyen (1,2,3)

(1) Computational Chemistry Research Group, Ton Duc Thang University, Ho Chi Minh City, Vietnam; (2) Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam; (3) Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium; (4) Department of Theoretical Physics, Ho Chi Minh City University of Science, Ho Chi Minh City, Vietnam

Amyloid beta (Aβ) oligomers are neurotoxic compounds that destroy the brain of Alzheimer’s disease patients. Recent studies indicated that the trimer is one of the most cytotoxic forms of low-weight Aβ oligomers. As there was limited information about the structure of Aβ trimer, either by experiment or computation, we determined in this work the structure of the 3Aβ11-40 oligomer for the first time using the temperature replica exchange molecular dynamics simulations with the appearance of explicit solvent. More than 20.0 µs of MD simulations were performed. The probability of the β-content and random coil structure of the solvated trimer amounts to 42 ± 6 and 49 ± 7 % that are in good agreement with experiments. Intermolecular interactions in central hydrophobic cores play a key role in stabilizing the oligomer. Intermolecular polar contacts between D23 and residues 24-29 replace the salt bridge D23-K28 to secure the loop region. The hydrophilic region of N-terminal is maintained by the intermolecular polar crossing contacts H13A-Q15B and H13B-Q15C. The difference in free energies of binding between the constituting monomers to the others is amounts to -36 ± 8 kcal/mol. The collision cross section of the representative structures of the trimer was computed to be 1330 ± 47 Å2, that is in good agreement with previous experiments.

Presenter: Ngo Son Tung