  The understanding of kinase structure is mostly based on protein
crystallography, which is limited by the requirement to trap molecules within a
crystal lattice. Therefore, characterisations of the conformational dynamics of
the activation loop in solution are important to enhance the understanding of
molecular processes related to diseases and to support the discovery of small
molecule kinase inhibitors. In this work, we demonstrated that long molecular
dynamics simulations exhaustively sampled all the conformational space of the
activation loop of the Aurora-A kinase and of the methane-thiosulfonate spin
label, introduced into the activation loop for the electron paramagnetic
measurements. MD was used to determine structural fluctuations, order
parameters and rotational correlation times of the motion of the activation
loop and of the MTSL. Theoretical data obtained were used as input for the
calculation of the room temperature 9 GHz continuous wave EPR of the Aurora-A
kinase in solution and the comparison between simulated and experimental date
revealed that the motion of the protein and spin label occurred on comparable
timescales. This work is a starting point for deeper experimental and
theoretical studies of the rotational and translational diffusion properties of
the Aurora-A kinase protein related to its biological activity.
