Automated X-ray Crystallography for Structural Genomics

University Of Calif-Lawrenc Berkeley Lab, Berkeley CA

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Abstract

Structural genomics seeks to rapidly expand the database of protein structures to permit the extract8on of much more information from the genomic sequence databases than is currently possible. This requires methods for the rapid determination of macromolecular structures using X-ray crystallography. At present the need for continual manual intervention makes rapid, minimally biased structure solution impossible. Therefore, it is imperative that crystallographic structure determination be automated in the near future. Unfortunately the crystallographic packages currently available, although possessing many powerful features, are collectively too diverse, out-data and lacking in the required functionality to be used as a solution to the problem. Major bottlenecks remain, especially during the process of model building and refinement. Therefore we will build a new system for crystallographic computing that will allow, amongst other things, the creation of new software that combines the powerful automation features of the SOLVE system, the computational flexibility of the Crystallography & NMR System and the automated map interpretation algorithms of the TEXTAL program. This system, named PHENIX, will permit tasks required for the computation of phases, automated map interpretation, model building and refinement, to be integrated with newly developed procedures for automated decision-making. Our ultimate goal is the development of a system that will take x-ray diffraction data and rapidly procedure biased atomic coordinates with little or no human intervention. The advantages of such a system extend beyond the realm of structural, genomics, allowing crystallographers to focus on more challenging biological problems.