Continuously heterogeneous hyper-objects in cryo-EM and 3-D movies of many temporal dimensions

Understand

Single particle cryo-electron microscopy (EM) is an increasingly popular method for determining the 3-D structure of macromolecules from noisy 2-D images of single macromolecules whose orientations and positions are random and unknown.

• One of the great opportunities in cryo-EM is to recover the structure of macromolecules in heterogeneous samples, where multiple types or multiple conformations are mixed together.
• Indeed, in recent years, many tools have been introduced for the analysis of multiple discrete classes of molecules mixed together in a cryo-EM experiment.
• However, many interesting structures have a continuum of conformations which do not fit discrete models nicely; the analysis of such continuously heterogeneous models has remained a more elusive goal.