This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Perhaps the most outstanding contribution of cryoEM is the ability to image macromolecular assemblies under nearly native conditions. However, the drawback to this is that the sample is often a mixture of macromolecules in different conformations, reflecting the natural and intrinsic behavior of a biological machine. Computational and biochemical approaches have sought to isolate these individual conformations, allowing for the processing and eventual reconstruction of several structures in the different conformations. This will provide us with a unique opportunity to visualize the structural dynamics of these machines in a series of snapshots, but stops short of answering more fundamental questions about the motions associated with the different conformations.