The Automation of Biological Crystallography Experiments at the Advanced Light SourceThomas Earnest The automation of the process of mounting, aligning, and unmounting crystals of biological molecules at synchrotron crystallography beamlines has been under development by many groups internationally over the past ~ five years, with significant progress made in the robotic mounting/unmounting under cryogenic and frost-free conditions. Less success has come for automated crystal recognition and alignment, although methods for the alignment of cryo-loops are being used at several sites. At LBNL and the ALS, a system for automated mounting has been in use since 2001 with a significant productive impact on users who have large numbers of crystals, either as part of high-throughput projects in structural genomics or drug discovery, or in extremely challenging projects where numerous crystals must be screened before sufficient-quality data can be collected. This system has improved and evolved, as well as propagated to other synchrotron sites, such as NSLS, CHESS, and APS. The utilization of an "open-source" framework for collaborators who are implementing the LBNL design allows for multi-party contributions to the further evolution of this system. Current challenges for future development, in addition to increasing reliability and robustness, include further integration into beamline control systems and experimental databases, accurate and reliable crystal recognition and alignment, remote monitoring/operation capabilities, pipelining into data processing and refinement, and high-level intelligent control of the process to achieve optimal data and performance. Acknowledgements: This research is supported by the National Institute of General Medical Sciences of the National Institutes of Health, including funding through the NIGMS Protein Structure Initiative. |