Effect of ligand binding state on the dynamics of conserved structural domains in kinesin

Atomistic simulations of kinesin molecular motor proteins offer a detailed view of the interplay between structure and dynamics. This provides the opportunity for a close analysis of the conserved motor protein "parts list" common across different kinesins. Such simulations can deepen understanding of how ATP hydrolysis drives the mechanical motion of the protein, translating to its biological function. Recent cryo-EM structures of the kinesin-3 family motor protein, KIF14, in multiple ligand-bound states (Benoit et al., 2021), provide high-quality structural templates for these studies. In this work, we present results from 10 ns all-atom simulations of the KIF14 motor protein head in complex with tubulin, comparing the APO, ADP, ADP + Pi, and ATP bound states. Each complex is modeled with ~280k atoms, including explicit waters. Our analysis focuses on how the motor head’s intrinsic dynamics and atomic environment differ across these states, highlighting the roles of key structural elements—Switch I, Switch II, and the P-loop—and the evolution of salt bridge formation. We establish high-quality simulation data for analyzing changes that occur in different stages of the kinesin catalytic cycle as a baseline for comparison across different kinesins.