Influence of Enantiomeric Inhibitors on the Dynamics of Acetylcholinesterase Measured by Elastic Incoherent Neutron Scattering

This work addresses the use of the Gaussian approximation as a common tool to extract atomic motions in proteins from elastic incoherent neutron scattering and whether improvements in data analysis and additional information can be obtained when going beyond that. We measured alphalactalbumin with different levels of hydration on three neutron backscattering spectrometers, to be able to resolve a wide temporal and spatial range for dynamics. We demonstrate that the Gaussian approximation gives qualitatively similar results to models that include heterogeneity, if one respects a certain procedure to treat the intercept of the elastic intensities with the momentum transfer axis. However, the inclusion of motional heterogeneity provides better fits to the data. Our analysis suggests an approach of limited heterogeneity, where including only two kinds of motions appears sufficient to obtain more quantitative results for the mean square displacement. Finally, we note that traditional backscattering spectrometers pose a limit on the lowest accessible momentum transfer. We therefore suggest that complementary information about the spatial evolution of the elastic intensity close to zero momentum transfer can be obtained using other neutron methods, in particular, neutron spin-echo together with polarization analysis.

Section: Comparison Between Summed Intensities and Mspfmentioning

confidence: 99%

Analysis of elastic incoherent neutron scattering data beyond the Gaussian approximation

Zeller

Telling

Zamponi

et al. 2018

Asymptotic analysis of quasielastic neutron scattering data from human acetylcholinesterase reveals subtle dynamical changes upon ligand binding

Peters

Kneller

2019

In this paper, we show that subtle changes in the internal dynamics of human acetylcholinesterase upon ligand binding can be extracted from quasielastic neutron scattering data by employing a nonexponential relaxation model for the intermediate scattering function. The relaxation is here described by a stretched Mittag-Leffler function, which exhibits slow power law decay for long times. Our analysis reveals that binding of a Huperzine A ligand increases the atomic motional amplitudes of the enzyme and slightly slows down its internal diffusive motions. This result is interpreted within an energy landscape picture for the motion of the hydrogen atoms.

Frequency domain modeling of quasielastic neutron scattering from hydrated protein powders: Application to free and inhibited human acetylcholinesterase

Peters

Kneller

2019

This article reports on a frequency domain analysis of quasielastic neutron scattering spectra from free and Huperzine-A-inhibited human acetylcholinesterase, extending a recent time domain analysis of the same experimental data [M. Saouessi et al., J. Chem. Phys. 150, 161104 (2019)]. An important technical point here is the construction of a semianalytical model for the resolution-broadened dynamic structure factor that can be fitted to the experimental spectra. We find comparable parameters as in our previous study and demonstrate that our model is sensitive to subpercent changes in the experimental data, which are caused by reversible binding of the inhibitor Huperzine A.