Structure-based drug design / Structure-based protein engineering / Applications of synchrotron radiation to the pharmaceutical industry / Protein crystallography in the pharmaceutical industry Protein Crystallography is Dead: Long Live Protein Crystallography!

I ventured into the field of protein crystallography in the early seventies, a few years after my undergraduate degree in physics from the Spanish educational system. This was a system where trespassing the boundaries of traditional disciplines was not encouraged. I was interested in biophysics as a general area of scientific enquiry and I needed to find a venue for my scientific interest and curiosity. Three years of independent work at the University of Salamanca, Spain, reading textbooks, papers and attending lectures in biochemistry, microbiology and genetics gave me enough background to move on. However, I needed to have a more formal training in the field. Complementing my scientific studies with studying English allowed me to come to the U.S. with a Fulbright Scholarship in 1972 to pursue graduate studies in biophysics at the University of Texas at Austin. There, I encountered protein crystallography as a worthwhile field of endeavor for a Ph. D. work, mentored by Profs. Marvin L. Hackert, Hugo Steinfink and Larry Fox. Six extraordinary years at Purdue University with Prof. Michael G. Rossmann completed my training, and I ended up using protein crystallography as a tool to design drugs in the pharmaceutical industry. A practical use for protein crystallography was an amazing, and certainly unforeseen, professional and technical development. In those years, the annual meetings of the ACA were vibrant with methodology sessions related to protein crystallography. All the different facets of protein crystallography were presented and discussed: the chemical trickery of growing crystals and preparing multiple isomorphous derivatives; methods and strategies of data collection and processing; the difficulties of extracting anomalous signal; the subtlety of using molecular replacement techniques to solve structurally related proteins; and discussions on the best pathway to a successful refinement. Of course, there were also sessions on novel structures, but these were relatively few. Protein Crystallography has become the unexpected victim of the ingenuity, inspiration and hard work of protein crystallographers themselves. Years of crystallographic