Structural Molecular Biology in the Post-Genome Sequencing Era
Recent advances in macromolecular crystallographic instrumentation and methodology have laid the foundation from which a production pipeline optimized towards the determination of large numbers of 3-dimensional protein structures can be constructed. It requires the detailed process analysis of the current approach to structure determination, which involves significant manual intervention and many trial-and-error steps. The transformation of this traditional approach into a linear series of high-throughput steps from sample characterization to structure solution is possible through the industrialization of the individual processes, which requires the automation, miniaturization, parallelization, and optimization of existing systems. The successful implementation of such a high-throughput automated system is an absolute prerequisite for the emerging field of structural genomics and will have significant impact on current approaches to structural biology.
Synchrotron radiation is the primary source of x-radiation for the determination of protein crystal structures and it is necessary to develop highly automated synchrotron beam lines, which must be operated within a sophisticated software and hardware environment. The Structural Molecular Biology resource at SSRL is currently developing the structure determination pipeline starting with the initial characterization of the frozen sample, followed by data collection, data reduction, phase determination, and model building.