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

In this study, diffusion constants [translational (DT) 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 A beta 40 and A beta 42 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 DT of 1.61 X 10(-6) cm(2)/s and 1.43 X 10(-6) cm(2)/s for A beta 40 and A beta 42, 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 A beta 40 and A beta 42 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 A beta 40 and A beta 42 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 A beta 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 A beta 40 and A beta 42. In addition, an effective rotational correlation time of A beta 40 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 S2 parameters for the central hydrophobic core, the loop region, and C-terminal domains of A beta 40 and A beta 42 are in accord with the previous studies. (c) 2009 American Institute of Physics. [doi:10.1063/1.3249609]