  Mapping conformational heterogeneity of macromolecules presents a formidable
challenge to X-ray crystallography and cryo-electron microscopy, which often
presume its absence. This has severely limited our knowledge of the
conformations assumed by biological systems and their role in biological
function, even though they are known to be important. We propose a new approach
to determining to high resolution the three-dimensional conformations of
biological entities such as molecules, macromolecular assemblies, and
ultimately cells, with existing and emerging experimental techniques. This
approach may also enable one to circumvent current limits due to radiation
damage and solution purification.
