The three-dimensional (3D) structures of molecules are very important for us to study the functions of molecules in many applications. Although the structures of most existing proteins are solved by x-ray crystallography or NMR spectroscopy, they do not give the \"full picture\" of a functional biological complex. The study of large macromolecular complexes, such as viruses, ion channels, the ribosome and other machines of various types, offers a more complete structural and functional description of the protein machinery. However, it becomes much more difficult for us to crystallize such large macromolecular complexes. Therefore, the non-crystallography technique using cryo-electron microscopy (CryoEM), commonly known as Single Particle Reconstruction, provides a powerful tool in revealing the structures of large complexes at sub-nanometer resolutions (5 - 10 A). Coupled with this technique are many algorithms newly developed in Image Processing, which are the main goal of our research in this project.

The following figure shows the overall procedure of this technique, starting from the two dimensional Cryo-EM images and/or the Protein Data Bank and ending up with the three dimensional pseudo-atomic structures of the large macromolecular complexes.