Challenges at the frontiers of structural biology (Reprinted from Trends in Biochemical Science, vol 12, Dec., 1999)

Knowledge of the three-dimensional structures of proteins is the key to unl ocking the full potential of genomic information. There are two distinct di rections along which cutting-edge research in structural biology is current ly moving towards this goal. On the one hand, tightly focused Long-term res earch in individual laboratories is Leading to the determination of the str uctures of macromolecular assemblies of ever-increasing size and complexity . On the other hand, large consortia of structural biologists, inspired by the pace of genome sequencing, are developing strategies to determine new p rotein structures rapidly, so that it will soon be possible to predict reas onably accurate structures for most protein domains. We anticipate that a s mall number of complex systems, studied in depth, will provide insights acr oss the field of biology with the aid of genome-based comparative structura l analysis.