Conformational fluctuations and rotational tumbling of proteins can be experimentally accessed with nuclear spin relaxation experiments. However, interpretation of molecular dynamics from the experimental data is often complicated, especially for molecules with anisotropic shape. Here, we apply classical molecular dynamics simulations to interpret the conformational fluctuations and rotational tumbling of proteins with arbitrarily anisotropic shape. The direct calculation of spin relaxation times from simulation data did not reproduce the experimental data. This was successfully corrected by scaling the overall rotational diffusion coefficients around the protein inertia axes with a constant factor. The achieved good agreement with experiments allowed the interpretation of the internal and overall dynamics of proteins with significantly anisotropic shape. The overall rotational diffusion was found to be Brownian, having only a short subdiffusive region below 0.12 ns. The presented methodology can be applied to interpret rotational dynamics and conformation fluctuations of proteins with arbitrary anisotropic shape. However, a water model with more realistic dynamical properties is probably required for intrinsically disordered proteins.

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences 117 20 Prague 6 Czech Republic

Research Program in Structural Biology and Biophysics Institute of Biotechnology University of Helsinki 00014 Helsinki Finland

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Accurate Simulations of Lipid Monolayers Require a Water Model with Correct Surface Tension

NMR structure of the C-terminal domain of TonB protein from Pseudomonas aeruginosa