English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The understanding of kinase structure is mostly based on proteincrystallography, which is limited by the requirement to trap molecules within acrystal lattice. Therefore, characterisations of the conformational dynamics ofthe activation loop in solution are important to enhance the understanding ofmolecular processes related to diseases and to support the discovery of smallmolecule kinase inhibitors. In this work, we demonstrated that long moleculardynamics simulations exhaustively sampled all the conformational space of theactivation loop of the Aurora-A kinase and of the methane-thiosulfonate spinlabel, introduced into the activation loop for the electron paramagneticmeasurements. MD was used to determine structural fluctuations, orderparameters and rotational correlation times of the motion of the activationloop and of the MTSL. Theoretical data obtained were used as input for thecalculation of the room temperature 9 GHz continuous wave EPR of the Aurora-Akinase in solution and the comparison between simulated and experimental daterevealed that the motion of the protein and spin label occurred on comparabletimescales. This work is a starting point for deeper experimental andtheoretical studies of the rotational and translational diffusion properties ofthe Aurora-A kinase protein related to its biological activity.

MD and EPR studies of the structure and dynamics of the MTSL spin-labelled activation loop of the Aurora-A kinase