Translational, rotational and internal dynamics of amyloid Β -peptides (AΒ40 and AΒ42) from molecular dynamics simulations

In this study, diffusion constants [translational (D_T) and rotational (D_R)], correlation times [rotational (τ_rot) and internal (τ_int)], and the intramolecular order parameters (S²) 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 cm² /s and 1.43× 10^-6 cm² /s for AΒ40 and A^Β42, 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 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 AΒ40 and AΒ42 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 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 AΒ40 and AΒ42. In addition, an effective rotational correlation time of AΒ40 is also computed at 18 °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 AΒ40 and AΒ42 are in accord with the previous studies.