TY - JOUR
T1 - Effects of All-Atom Molecular Mechanics Force Fields on Amyloid Peptide Assembly
T2 - The Case of Aβ16-22Dimer
AU - Man, Viet Hoang
AU - He, Xibing
AU - Derreumaux, Philippe
AU - Ji, Beihong
AU - Xie, Xiang Qun
AU - Nguyen, Phuong H.
AU - Wang, Junmei
N1 - Publisher Copyright:
© 2019 American Chemical Society. All rights reserved.
PY - 2019/2/12
Y1 - 2019/2/12
N2 - We investigated the effects of 17 widely used atomistic molecular mechanics force fields (MMFFs) on the structures and kinetics of amyloid peptide assembly. To this end, we performed large-scale all-atom molecular dynamics simulations in explicit water on the dimer of the seven-residue fragment of the Alzheimer's amyloid-β peptide, Aβ16-22, for a total time of 0.34 ms. We compared the effects of these MMFFs by analyzing various global reaction coordinates, secondary structure contents, the fibril population, the in-register and out-of-register architectures, and the fibril formation time at 310 K. While the AMBER94, AMBER99, and AMBER12SB force fields do not predict any β-sheets, the seven force fields, AMBER96, GROMOS45a3, GROMOS53a5, GROMOS53a6, GROMOS43a1, GROMOS43a2, and GROMOS54a7, form β-sheets rapidly. In contrast, the following five force fields, AMBER99-ILDN, AMBER14SB, CHARMM22*, CHARMM36, and CHARMM36m, are the best candidates for studying amyloid peptide assembly, as they provide good balances in terms of structures and kinetics. We also investigated the assembly mechanisms of dimeric Aβ16-22 and found that the fibril formation rate is predominantly controlled by the total β-strand content.
AB - We investigated the effects of 17 widely used atomistic molecular mechanics force fields (MMFFs) on the structures and kinetics of amyloid peptide assembly. To this end, we performed large-scale all-atom molecular dynamics simulations in explicit water on the dimer of the seven-residue fragment of the Alzheimer's amyloid-β peptide, Aβ16-22, for a total time of 0.34 ms. We compared the effects of these MMFFs by analyzing various global reaction coordinates, secondary structure contents, the fibril population, the in-register and out-of-register architectures, and the fibril formation time at 310 K. While the AMBER94, AMBER99, and AMBER12SB force fields do not predict any β-sheets, the seven force fields, AMBER96, GROMOS45a3, GROMOS53a5, GROMOS53a6, GROMOS43a1, GROMOS43a2, and GROMOS54a7, form β-sheets rapidly. In contrast, the following five force fields, AMBER99-ILDN, AMBER14SB, CHARMM22*, CHARMM36, and CHARMM36m, are the best candidates for studying amyloid peptide assembly, as they provide good balances in terms of structures and kinetics. We also investigated the assembly mechanisms of dimeric Aβ16-22 and found that the fibril formation rate is predominantly controlled by the total β-strand content.
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U2 - 10.1021/acs.jctc.8b01107
DO - 10.1021/acs.jctc.8b01107
M3 - Article
C2 - 30633867
AN - SCOPUS:85061270362
SN - 1549-9618
VL - 15
SP - 1440
EP - 1452
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 2
ER -