Translational, rotational and internal dynamics of amyloid β-peptides (Aβ40 and Aβ42) from molecular dynamics simulations

摘要

In this study, diffusion constants [translational (DT) and rotational (DR)], correlation times [rotational (τ_(rot)) and internal (τ_(int))], and the intramolecular order parameters (S~2) of the Alzheimer amyloid-β peptides Aβ40 and Aβ42 have been calculated from 150 ns molecular dynamics simulations in aqueous solution. The computed parameters have been compared with the experimentally measured values. The calculated D_T of 1.61×10~(-6) cm~2 / s and 1.43×10~(-6) cm~2 / s for Aβ40 and Aβ42, respectively, at 300 K was found to follow the correct trend defined by the Debye–Stokes–Einstein relation that its value should decrease with the increase in the molecular weight. The estimated DR for Aβ40 and Aβ42 at 300 K are 0.085 and 0.071 ns~(-1), respectively. The rotational (C_(rot)(t)) and internal (C_(int)(t)) correlation functions of A40 and A42 were observed to decay at nano- and picosecond time scales, respectively. The significantly different time decays of these functions validate the factorization of the total correlation function (C_(tot)(t)) of Aβ peptides into Crot(t) and Cint(t). At both short and long time scales, the Clore–Szabo model that was used as Cint(t) provided the best behavior of Ctot(t) for both Aβ40 and Aβ42. In addition, an effective rotational correlation time of Aβ40 is also computed at 18 ℃ and the computed value (2.30 ns) is in close agreement with the experimental value of 2.45 ns. The computed S~2 parameters for the central hydrophobic core, the loop region, and C-terminal domains of Aβ40 and Aβ42 are in accord with the previous studies.