Protein nanomachines made of multiple protein molecules are highly dynamic during their actions on their functional targets, sometime called substrates. Dynamics of these large protein nanomachines of more than megadalton molecular weight are refractory to structural analysis by existing technology like X-ray crystallography and nuclear magnetic resonance spectroscopy. Cryo-electron microscopy (cryo-EM), an emerging technology for high-resolution structure determination, has potential to visualize dynamics of large protein nanomachines, but the existing cryo-EM reconstructions of highly dynamic structures have been limited to moderate to low resolution.