a1 The Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA
a2 Department of Biological Sciences, Columbia University, New York, NY, USA
This essay gives the autho's personal account on the development of concepts underlying single-particle reconstruction, a technique in electron microscopy of macromolecular assemblies with a remarkable record of achievements as of late. The ribosome proved to be an ideal testing ground for the development of specimen preparation methods, cryo-EM techniques, and algorithms, with discoveries along the way as a rich reward. Increasingly, cryo-EM and single-particle reconstruction, in combination with classification techniques, is revealing dynamic information on functional molecular machines uninhibited by molecular contacts.
c1 Author for correspondence: Dr J. Frank, The Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, P&S BB 2-221, 650 West 168th Street, New York, NY 10032, USA. Email: email@example.com