The Scripps Research Institute, La Jolla, CA, USA, and ETH Zürich, Zürich Switzerland
The determination of the human genome and the genomes of a large number of other species has awakened big expectations in many different fields, including agriculture, nutrition and healthcare. However, much of the realization of these anticipated advances will have to be based on detailed knowledge of the proteome and other gene products of the organisms of interest, in addition to the rapidly expanding protein sequence universe derived by annotation of the genomic DNA sequences. More specifically one aims for coverage of the protein universe derived from the DNA sequences with three-dimensional structures, which can then provide a platform for rational drug discovery and similar applications.
My research team makes use of solution nuclear magnetic resonance (NMR) spectroscopy for protein structure determination and for collecting supplementary function-related data. NMR has for many years shared its role as a principal technique in the structural biology of proteins and nucleic acids with X-ray diffraction in single crystals. In today’s post-genomic era, structural biologists using these techniques are faced with new opportunities and challenges, following novel strategies of “structural genomics”. In this venture the NMR method is unique, when compared to structure determination by X-ray crystallography, in that atomic resolution structures and other function-related data can be obtained under solution conditions close to the physiological milieu in body fluids. By generating information on protein structure, stability, dynamics and intermolecular interactions in solution, NMR has an exciting role in the longer-term challenge leading from the expanding protein universe to new insights into protein functions and chemical biology.