Virus crystallography and structural virology: a personal perspective

My first experiences with crystallography were as a graduate student at the University of Glasgow determining the structure of aromatic hydrocarbons using only primitive hand calculation techniques. I had my first experience using electronic computers as a post-doc in the lab of William Lipscomb in Minnesota. That gave me a good preparation for the structure determination of haemoglobin with Max Perutz in Cambridge. The discovery of the conserved globin fold had a major impact on my subsequent activities. It also provided the foundation for the development of the molecular replacement method and non-crystallographic symmetry electron density averaging that was essential for the structure determination of simple icosahedral viruses. The structure determination of a common cold virus was also a major stimulus for the study of more complex viruses and the development of the use of cryo-electron microscopy. This provided the basis for the investigation of lipid-enveloped viruses such as Sindbis virus and dengue virus. It also provided the technology for the study of bacteriophage DNA packaging motors and the mechanisms of infection by tailed and untailed phages.