Quasielastic neutron scattering in biology: Theory and applications

Abstract

Neutrons scatter quasielastically from stochastic, diffusive processes, such as overdamped vibrations, localized diffusion and transitions between energy minima. In biological systems, such as proteins and membranes, these relaxation processes are of considerable physical interest. We review here recent methodological advances and applications of quasielastic neutron scattering (QENS) in biology, concentrating on the role of molecular dynamics simulation in generating data with which neutron profiles can be unambiguously interpreted. We examine the use of massively-parallel computers in calculating scattering functions, and the application of Markov state modeling. The decomposition of MD-derived neutron dynamic susceptibilities is described, and the use of this in combination with NMR spectroscopy. We discuss dynamics at very long times, including approximations to the infinite time mean-square displacement and nonequilibrium aspects of single-protein dynamics. Finally, we examine how neutron scattering and MD can be combined to provide information on lipid nanodomains. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.

Dynamics of proteins in solution

“…The full hierarchy of motions ranging from translational and rotational diffusion of the entire molecule over large-scale domain motions down to localized dynamics of backbone and side-chains (see section ‘Protein dynamics on hierarchical time- and length-scales’) is represented in the quasielastic spectrum S ( q , ω ) in a convoluted way. While qualitative dynamical changes can be already observed from the spectra alone, extracting more detailed and quantitative information on the underlying dynamics requires modeling and data fitting, and potentially comparison with simulation (Vural et al ., 2017). In the following sections, we outline the basic modeling approaches to address the different hierarchical levels of protein dynamics.…”

“…We do not further consider such vibrational motions in this review, because they appear less specific to aspects of protein dynamics in solution. For further details, we refer the reader to other reviews covering protein vibrations from the perspective of various specific techniques (Vogel and Siebert, 2000; Parak, 2003 a ; Nibbering et al ., 2005; Vural et al ., 2017).…”

Investigating Structure and Dynamics of Proteins in Amorphous Phases Using Neutron Scattering

“…At a given $\widehat{bold\mathbf{q}}$, the corresponding length $\sim \frac{2\pi }{q}$ can be considered to be the probability that a given particle is within the length scale of the measurement or calculation within the time/energy resolution of the instrument. Further informative descriptions of the calculation of  < x 2  > from MD trajectories and the relationship between the analysis of neutron scattering data and MD simulations can be found in the literature [74], [75], [76].…”

“…Therefore, this article is not meant to be an inclusive review of the extensive literature of the measurement of protein dynamics using neutron scattering. Interested readers are encouraged to consult classical papers [91], [92], [93], [94], reviews [76], [95], [96] and exciting neutron scattering studies involving hydration [71], [97], [98], [99], [100], [101], [102], [103], [104], [105], and important studies of dissacharides and polyols in solution [106], [107] and with proteins [83], [108], [109].…”

Determination of Dynamical Heterogeneity from Dynamic Neutron Scattering of Proteins

“…Incoherent neutron-scattering methods and numerical simulation have been widely used to determine motional displacements in proteins . Enormous progress has been made in measuring, interpreting, and calculating mean-square motional displacements (MSDs) as a function of temperature, the level of hydration, and the level and type of solution and of applied pressure on the protein (10,20,25,28,29). Because the incoherent scattering cross section of hydrogen (H) is large compared with that of other nuclei, the observed MSDs are dominated by those of H. There are typically 1500 H in a protein.…”