High-resolution structures of biological molecules obtained through x-ray crystallography provide among the most important sources of data for understanding function and mechanism. However, the process of crystallization presents a major bottleneck since hundreds or thousands of conditions need to be evaluated to find initial crystal """"""""hits"""""""" that, through iterative rounds of optimization, become useful for structure determination. We propose to acquire a system for the automated optimization of crystallization experiments in order to expand the number of crystallization trials that can be effectively performed in a rapid and reproducible manner, thus to dramatically enhance the rate of success. Columbia University has a large and vibrant structural biology community, involved in numerous projects of substantial biomedical importance, and many members play leading role in NIH-funded high-throughput crystallography projects that will directly benefit from this instrument. After substantial due diligence, we have opted to propose the acquisition of an Eppendorf epMotion 5075 TMX liquid handling system for the automated generation of optimization screens to generate diffraction-quality crystals for structure determination.
