Determination of Dynamical Heterogeneity from Dynamic Neutron Scattering of Proteins

Abstract

Motional displacements of hydrogen (H) in proteins can be measured using incoherent neutron-scattering methods. These displacements can also be calculated numerically using data from molecular dynamics simulations. An enormous amount of data on the average mean-square motional displacement (MSD) of H as a function of protein temperature, hydration, and other conditions has been collected. H resides in a wide spectrum of sites in a protein. Some H are tightly bound to molecular chains, and the H motion is dictated by that of the chain. Other H are quite independent. As a result, there is a distribution of motions and MSDs of H within a protein that is denoted dynamical heterogeneity. The goal of this paper is to incorporate a distribution of MSDs into models of the H incoherent intermediate scattering function, I(Q,t), that is calculated and observed. The aim is to contribute information on the distribution as well as on the average MSD from comparison of the models with simulations and experiment. For example, we find that simulations of I(Q,t) in lysozyme are well reproduced if the distribution of MSDs is bimodal with two broad peaks rather than a single broad peak.

Analysis of elastic incoherent neutron scattering data beyond the Gaussian approximation

“…24 Meinhold et al used a Weibull distribution, 25 and Peters and Kneller used a gamma distribution 26 based on the work of Kneller and Hinsen. 27 Most recently, a bimodal Gaussian distribution was investigated by Vural et al 28 Doster also addressed the issue of protein dynamical heterogeneity by suggesting three different approaches to it. 29 His main conclusion was to say that data can be fitted as successful when heterogeneity is reduced to two kinds of molecular processes, one corresponding to translational and the other to rotational (coming mainly from methyl groups) motions, the latter being non-Gaussian scattering processes.…”

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

“…Meinhold et al used a Weibull distribution and Peters and Kneller a Gamma distribution . Most recently, a bimodal Gaussian distribution was introduced by Vural et al All of these methods represent interesting aspects and permit a better although more complex description of the data. In a representative manner, we applied the model recently developed by Peters and Kneller that, unlike the MSD, permits the inclusion of data over the entire Q -range.…”