This proposal is directly applicable to the Protein Structure Initiative. A major bottleneck in the initiative is the capability to obtain quality diffractable protein crystals for structure elucidation. The automated DCCS system described in this proposal has been designed to minimize the effects of the protein crystal bottleneck. The automated DCCS system has the capacity to screen 100 independent conditions in parallel. The innovation of this system over traditional methods of protein crystallography is that the automated DCCS system can monitor the crystallization chamber using stereomicroscopic and ultra high resolution video systems capable of resolving crystals 20-40 microns in size and can control the equilibration process during the experiment through the use of motors that pump volumes of as little as 4 microliters per pulse, such to optimize crystal screening in a shorter period of time, and more thoroughly. This technology should reduce the time required to determine suitable conditions for crystallization and increase the number of protein structures available for structure based rational drug design. PROPOSED COMMERCIAL APPLICATION: The commercial applications are the marketing of this new crystallization system and a contractual service for pharmaceutical companies and research organizations. The service will crystallize proteins of interest, determine their structures and provide consultant services for drug development.
