Structural insight into Aurora A kinase based on molecular dynamics simulations

Aurora A kinase is one of the important targets for cancer and has inhibitors in clinical trials and due its high numbers of crystal structures that are deposited in RCSB database make it as good target to understand its mechanism. I have studied Aurora A kinase domain with its important residues using molecular dynamics simulations (MD simulations), and deeply I focused on regions as DFG motif, alpha-C-helix, HRD motif and activation loop. Two system of Aurora A complexes (protein-inhibitor) were selected to evaluate their flexibility and understand all changes and screening important interactions. The first complex of Aurora A which is described as inactive form and its DFG-out is in vertical state, and second complex of Aurora A kinase and its DFG available as DFG-in, and from multiple of MD simulations runs I identified important structural changes and transitions, The result provides clarification to understand flexibility of Aurora A for active and inactive forms and other nearest parts. The work was performed using MD simulations in nano to micro-second, and the result was compared with reported crystal structures of Aurora A as monomers and dimers.