Molecular Dynamics Simulations of a Powder Model of the Intrinsically Disordered Protein Tau

The Journal of Physical Chemistry. B
Yann FichouD J Tobias

Abstract

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" clus...Continue Reading

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Citations

Apr 1, 2016·BMC Genomics·Frederik SündermannReginald O Morgan
Jun 15, 2016·The Journal of Physical Chemistry Letters·Daniela RussoGaetano Campi
Feb 18, 2017·The Journal of Physical Chemistry Letters·Yangzhong QinDongping Zhong
Mar 5, 2020·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Alexander KrahPeter J Bond

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