Motional heterogeneity in human acetylcholinesterase revealed by a non-Gaussian model for elastic incoherent neutron scattering

Abstract

We study the dynamical transition of human acetylcholinesterase by analyzing elastic neutron scattering data with a simulation gauged analytical model that goes beyond the standard Gaussian approximation for the elastic incoherent structure factor [G. R. Kneller and K. Hinsen, J. Chem. Phys. 131, 045104 (2009)]. The model exploits the whole available momentum transfer range in the experimental data and yields not only a neutron-weighted average of the atomic mean square position fluctuations, but also an estimation for their distribution. Applied to the neutron scattering data from human acetylcholinesterase, it reveals a strong increase of the motional heterogeneity at the two transition temperatures T = 150 K and T = 220 K, respectively, which can be located with less ambiguity than with the Gaussian model. We find that the first transition is essentially characterized by a change in the form of the elastic scattering profile and the second by a homogeneous increase of all motional amplitudes. These results are in agreement with previous combined experimental and simulation studies of protein dynamics, which attribute the first transition to an onset of methyl rotations and the second to more unspecific diffusion processes involving large amplitude motions.

Motional displacements in proteins: The origin of wave-vector-dependent values

“…This opens the way to using the Q dependence of r 2 to test models of distribution of the (r j ) 2 without concern that the Q dependence could arise from other factors. Several studies aimed at extracting the distribution of r 2 values, or moments of the distribution, have already been proposed [3,24,28,29,40]. For example, Nakagawa et al [40] find a bimodal distribution of MSDs is consistent with data.…”

“…9 has a peak at r 2 ≃ 0.25Å 2 and a tail reaching up to r 2 = 3 − 4Å 2 . A much better fit was found to the observed EISF out to Q = 4.5Å −1 using a Gamma distribution than using a single average r 2 [29]. Furthermore, when a distribution of r 2 was used, the average r 2 obtained was also much larger and the dynamical transition temperature, T D , more consistently determined.…”

“…Peters and Kneller [29] have made fits to observed EISF using a model in which the r 2 have a Gamma distribution [28]. In this distribution a large fraction of the H have small r 2 values with a tail in the distribution reaching large r 2 values.…”

“…In further work, Peters and Kneller [29] fitted the Gamma distribution model of S i (Q, ω = 0), to S i (Q, ω = 0) of human acetylcholinesterase (hSChE) observed on 3 neutron spectrometers at the Institut Laue-Langevin, IN6 (W = 50 µeV), IN13 (W = 8 µeV) and IN16 (W = 0.9 µeV). They were able to obtain good fits to the data for which a Gaussian with a single r 2 , as in Eq.…”

Direct comparison of elastic incoherent neutron scattering experiments with molecular dynamics simulations of DMPC phase transitions

“…We have therefore also used a non-Gaussian model, presented in [47], to extract mean square atomic position fluctuations (MSPF) from the whole Q range. Thus two experimental determinations of the dynamical amplitudes can be compared with the MSD from the MD simulations, in all cases taking into account the energy resolution of the spectrometers.…”