Three-dimensional structure determination of macromolecules and macromolecu
lar complexes is an integral part of understanding biological functions. Fo
r large protein and macromolecular complexes structure determination is oft
en performed using electron cryomicroscopy where projection images of indiv
idual macromolecular complexes are combined to produce a three-dimensional
reconstruction. Single particle methods have been devised to perform this s
tructure determination for macromolecular complexes with little or no under
lying symmetry. These computational methods generally involve an iterative
process of aligning unique views of the macromolecular images followed by d
etermination of the angular components that define those views. In this rev
iew, this structure determination process is described with the aim of clar
ifying a seemingly complex structural method. (C) 2001 Federation of Europe
an Biochemical Societies. Published by Elsevier Science B.V. All rights res
erved.