Molecular Dynamics Simulation of KIF14 Kinesin Motor Protein Structural Subdomains*

Atomistic simulations of the mitotic kinesin motor protein KIF14, a subfamily member of the kinesin-3 family, can provide a fine-grained look at its intrinsic motion during cell mitosis, deepening mechanistic insight into the coupling of ATP hydrolysis to the protein’s mechanical motion and biological function. Cryo-EM structures for this protein in four different ligand-bound states have recently been reported by Benoit et al. (Nat. Commun. 2021), providing high-quality structural starting points for the simulations. Here we report results from 10 ns all-atom simulations of solvated KIF14 in complex with the α and β subunits of its substrate tubulin microtubule track in the APO, ADP, ADP + P_i, and ATP ligand-bound states of its catalytic cycle.  All simulations were performed using the NAMD 3.0 molecular dynamics simulation code, with ~280k atoms, 1 fs timestep, and explicit TIP3P waters. Downstream trajectory analysis was performed to understand kinesin conformational changes in the motor head-microtubule complex in various ligand-bound states associated with an “open” configuration. These changes are analyzed in terms of the dynamics of the motor head subdomain “parts list,” such as  Switch I, Switch II, and the P-loop.