Automation

The Physical Biosciences Division in partnership with the Engineering Division's Bioinstrumentation Group is working to develop new technologies to automate key processes across the division. Recent projects include a crystal robot for high throughput protein crystallization experiments and an automounter robot for automated crystal mounting for beamline data collection.

In the area of automated software, PBD researchers are developing a system for automated data collection and processing. Recently the first component of this system has been implemented. This permits automatic screening of 112 cryo-cooled samples for diffraction quality, and display of the results in summary form. Samples are placed on the goniometer by a robotic arm, and automatically centered in the X-ray beam using optical microscopy. X-ray diffraction data are piped to the MOSFLM data processing program, and the results are deposited in a database. The system prioritizes data collection based on the quality score for each crystal and optimum data collection parameters are determined for subsequent data collection and processing.

Currently, our scientists are using software called DCS (distributed control system) that is written in JAVA, C++, and C. This includes capabilities for crystal mounting, alignment and data collection. Additionally, protocols can be scripted into the software that allow for mounting, alignment, and data collection of one or more images on all 64 (or 112) crystals in the sample shipping container inside the hutch.

Division researchers plan to continue to develop automation systems on the beamlines. The next phase is to design and implement "expert" software to control and optimize data collection. When accomplished, this will ultimately lead to an increase in beamline efficiency and data accuracy. In routine cases it will be possible for data to be collected, processed and analyzed without the user even being present at the synchrotron. Our ultimate goal is for automation to enable a 'crystals in, structures out' capability.

One of our primary goals is the creation of a novel software package called PHENIX (Python-based Hierarchical Environment for Integrated Xtallography). This software is being developed as part of an international collaboration, funded by NIH and headed by the CCI group. Those currently involved are: Tom Terwilliger (Los Alamos National Laboratory), Randy Read (University of Cambridge, U.K.), Tom Ioerger and Jim Sacchettini (Texas A&M University).

The availability of the PHENIX program in the future will be important for Structural Genomics projects, which require automated structure solution to analyze large volumes of data. The CCI is therefore part of the Berkeley Structural Genomics Center. Our role is to provide the computational tools to rapidly solve structures once the experimental data has been collected.

In order to facilitate the development of PHENIX we are creating a programming toolbox that contains fast, portable C++ code for many of the basic algorithms used in X-ray crystallography. This Computational Crystallography toolbox (cctbx) is also intended to allow other developers to efficiently implement crystallographic applications that exploit modern programming techniques. The cctbx is now available as an open-source package at SourceForge. The code is designed with an open and flexible architecture to promote extendibility and easy incorporation into other software
environments.

In order to streamline structure solution the collection and processing of the diffraction data must also be automated. We are developing software for this purpose in collaboration with Thomas Earnest at the Advanced Light Source. Our goal is together provide a system that will permit researchers to collect, process and analyze their data in a highly automated way at synchrotron sites. This will speed up structure solution, but most importantly make very efficient use of the beamline facilities.