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

Abstract

In this study, diffusion constants [translational (D(T)) and rotational (D(R))], correlation times [rotational (tau(rot)) and internal (tau(int))], and the intramolecular order parameters (S(2)) of the Alzheimer amyloid-beta peptides Abeta40 and Abeta42 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 x 10(-6) cm(2)/s and 1.43 x 10(-6) cm(2)/s for Abeta40 and Abeta42, 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 D(R) for Abeta40 and Abeta42 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 Abeta40 and Abeta42 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 Abeta peptides into C(rot)(t) and C(int)(t). At both short and long time scales, the Clore-Szabo model that was used as C(int)(t) provided the best behavior of C(tot)(t) for both Abeta40 and Abeta42. In addition, an effective rotational correlation time of Abeta40 is also computed at 18 degrees C 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 Abeta40 and Abeta42 are in accord with the previous studies.