W0323

Automated Structure Analysis of Proteins: A Software Architecture for High-Throughput Structure Determination. Ashley Deacon¹, Fred Bertsch¹, Frank von Delft², Timothy McPhillips¹, Glen Spraggon³ and Peter Kuhn¹, ¹Stanford Synchrotron Radiation Laboratory (SSRL), 2575 Sand Hill Road, Menlo Park, CA 94025, ²The Scripps Research Institute (TSRI), 10550 N. Torrey Pines Road, La Jolla, CA 92037, ³Genomics Institute if the Novartis Research Foundation (GNF), 3115 Merryfield Row, La Jolla, CA 92121.

The Structure Determination Core (SDC) of the Joint Center for Structural Genomics (JCSG) is centered at Stanford Synchrotron Radiation Laboratory (SSRL). The SDC is developing the Automated Structure Analysis of Proteins (ASAP) system, which will dramatically increase the throughput of SSRL beam lines. The system will be capable of solving several hundred protein structures each year. ASAP will use robotic hardware to mount crystals from large capacity storage cassettes and then use automated software for rapid crystal alignment. It will evaluate a set of crystals and select the best ones for data collection. ASAP will be able to run an extensive selection of crystallographic software without human intervention. It will simultaneously try a variety of algorithms and select the best results. ASAP will use machine learning to decide which algorithms are most likely to give the best results at each step in process. ASAP will integrate the experimental and computational aspects of crystallography, such that results generated by the data analysis can feedback and optimize the data collection. ASAP will support an arbitrary number of beam line and computing resources and it will be possible to dynamically add new crystallographic algorithms as they become available. ASAP will efficiently schedule the allocation of all beam line and computational resources between multiple projects and if possible it will execute them in parallel. The proposed architecture for the ASAP system will be described.

SSRL is funded by DOE (Office of Basic Energy Sciences). The SSRL Structural Molecular Biology program is funded by NIH (National Center for Research Resources), DOE (Office of Biological and Environmental Research) and NIH (National Institute of General Medical Sciences).