MAX T. ROGERS DISTINGUISHED LECTURESHIP IN CHEMISTRY
(Conferences / Seminars / Lectures)
The MAX T. ROGERS DISTINGUISHED LECTURESHIP welcomes a lecture by Professor Raymond Charles Stevens, Departments of Molecular Biology and Chemistry, The Scripps Research Institute, La Jolla, CA
Adventures in High Throughput Structure Based Drug Discovery
During the past 10 years significant progress has been made in developing novel high throughput structural biology technologies for protein cloning, expression, purification, crystallization, crystal imaging, synchrotron beamline data collection, NMR analysis, and structure determination/analysis. These developments are largely a result of the U.S. NIGMS Protein Structure Initiative, and efforts in Europe (e.g. SPINE) and Japan (e.g. Protein-3000). At The Scripps Research Institute, we have been able to miniaturize, automate and parallelize the structural biology processes using nanoliter volume technologies and more recently with human membrane proteins using lipidic cubic phase and pre-crystallization tools. The majority of these developments have now been commercialized and are being used by both traditional structural biology labs and structural genomics centers. Accordingly, significantly smaller amounts of materials can be used at all steps, and more parallel experiments can be engineered (genetically and mechanically) within the same space and time constraints, at lower costs. Application and results from these efforts towards entire proteomes (e.g. T. maritima, SARS), enzyme pathways/families (e.g. catecholamine biosynthesis, botulinum neurotoxins), high value drug targets (e.g. DPPIV, PAL) including G-protein Coupled Receptors (GPCRs) are now starting to emerge and will be presented. From these efforts, multiple biotechnology companies have emerged and generated marketed drugs or compounds now in the clinic to treat a number of human diseases (e.g. Syrrx, MemRx, Receptos, RuiYi). Lastly, lessons that we have learned from the past 10 years leads us to conclude that integration of the new individual technologies will significantly increase the levels of structure determination successes and throughput than is currently possible today.