Molecular Dynamics Simulations of a Powder Model of the Intrinsically Disordered Protein Tau.
The tau protein, whose aggregates are involved in Alzheimer's disease, is an intrinsically disordered protein (IDP) that regulates microtubule activity in neurons. An IDP lacks a single, well-defined structure and, rather, constantly exchanges among multiple conformations. In order to study IDP dynamics, the combination of experimental techniques, such as neutron scattering, and computational techniques, such as molecular dynamics (MD) simulations, is a powerful approach. Amorphous hydrated powder samples have been very useful for studying protein internal dynamics experimentally, e.g., using neutron scattering. Thus, there is demand for realistic in silico models of hydrated protein powders. Here we present an MD simulation analysis of a powder hydrated at 0.4 g water/g protein of the IDP tau in the temperature range 20-300 K. By comparing with neutron scattering data, we identify the protein-water interface as the predominant feature determining IDP dynamics. The so-called protein dynamical transition is shown to be attenuated, but not suppressed, in the parts of the protein that are not exposed to the solvent. In addition, we find similarities in the mean-squared displacements of the core of a globular protein and "dry" clusters formed by the IDP in hydrated powders. Thus, the ps to ns dynamics of proteins in hydrated powders originate mainly from those residues in contact with solvent. We propose that by measuring the dynamics of protein assemblies, such as aggregates, one might assess qualitatively their state of hydration.
Université Grenoble Alpes, IBS, F-38044 Grenoble, France.|CNRS, IBS, F-38044 Grenoble, France.|CEA, IBS, F-38044 Grenoble, France.
Yann
Y
Fichou
Max-Planck-Institut für Kohlenforschung , D-45470 Mülheim an der Ruhr, Germany.
Matthias
M
Heyden
Institut Laue-Langevin , 38000 Grenoble, France.
Giuseppe
G
Zaccai
Université Grenoble Alpes, IBS, F-38044 Grenoble, France.|CNRS, IBS, F-38044 Grenoble, France.|CEA, IBS, F-38044 Grenoble, France.
Martin
M
Weik
Department of Chemistry, University of California , Irvine, California 92697-2025, United States.
Douglas J
DJ
Tobias
D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011208:Powders; D016875:tau Proteins / Q000737:chemistry*
D011208:Powders; D016875:tau Proteins