Conformational Proteomics of Macromolecular Architecture: Approaching the Structure of Large Molecular Assemblies and their Mechanisms of Action

This paper traces the beginnings of structural virology, from the early 1950's to the presentation of the Caspar-Klug theory of virus structure in 1962. It focuses primarily on the virus research of Francis Crick, James Watson, Rosalind Franklin, Aaron Klug, and Donald Caspar. Collaborative efforts in X-ray crystallography and electron microscopy in combination with intellectual triggers from the Art world provided the soil from which the early theories of virus structure grew and matured.
Keywords: Virus structure, Caspar-Klug theory, geodesic domes, tensegrity, self-assembly, quasi-equivalence, history of molecular biology, 5-fold symmetry
In the 1950's and early 1960's the field of structural virology blossomed. Theoretical speculation was driven by the technical development in biochemistry, electron microcopy, and X-ray crystallography. The improved methodology for data collection and evaluation made it possible to explore the structure of large molecular assemblies, and among them viruses. In the early to mid 1950's, Francis Crick and James Watson speculated that "spherical viruses" possess cubic symmetry and quite possibly icosahedral symmetry. Using single crystal X-ray diffraction, Donald Caspar confirmed the icosahedral symmetry of Tomato Bushy Stunt Virus (TBSV or BSV). Watson showed that the rod-shaped Tobacco Mosaic Virus (TMV) is helical and Rosalind Franklin later determined its exact helical parameters. Aaron Klug found that Turnip Yellow Mosaic Virus (TYMV) and poliovirus also possess icosahedral symmetry. The Crick-Watson theory of virus structure applied best to 60 equivalently placed, identical...