Nicholas K. Sauter, Carl W. Cork, Ralf W. Grosse-Kunstleve, John R.
Taylor, Thomas N. Earnest, and Paul D. Adams
Lawrence Berkeley National Laboratory, Berkeley, CA 94720
Abstract:
With structural genomics programs and
drug discovery efforts producing large numbers of macromolecular
crystals, increasing demands are being placed on synchrotron beamlines.
To facilitate high-throughput crystallography, we are developing new
methods for achieving automation. One such development is LABELIT (the
Lawrence Berkeley Lab Indexing Toolbox),
a program with new procedures for autoindexing diffraction patterns.
Specifically, the program represents an improvement in three areas: 1)
LABELIT can tolerate inaccuracies in the given position of the incident
beam of up to several millimeters; 2) A check is made to confirm that
the deduced unit cell is not an integer multiple of the true unit cell;
and 3) A different approach is used to identify the Bravais symmetry to
better accommodate experimental uncertainty. These methods help to
correct failures commonly experienced during indexing, and increase the
overall success rate of the process. Moreover, LABELIT produces its
results without any requirement for computer graphics intervention. It
is presently running as a background process at beamlines 5.0.1, 5.0.2,
and 5.0.3 of the Advanced Light Source, and will soon be available at
beamlines 8.2.1 and 8.2.2. Beamline users can see the results through a
simple web interface. General users can upload data and experiment with
LABELIT at our website,
http://cci.lbl.gov/labelit.
Rapid indexing without the need for visual inspection is just one important ingredient for overall automation. Beamlines 5.0.1, 5.0.2, and 5.0.3 have been equipped with robotic mounters to transfer cryocooled samples to the goniometer. Software tools to complement the robot are in place at the beamline, and are also still evolving. These include high-level graphical controls to rapidly screen 96 samples, rank them by diffraction quality, and proceed with the collection of full data sets. It is intended that minimal input will be required for this type of operation, as diffraction experiments can be automatically orchestrated by underlying software modules. Unattended, the AutoScreen module will center each crystal in the X-ray beam by analyzing videomicrographs, acquire two diffraction snapshots, index the lattice with LABELIT, and compute the Bravais symmetry. An AutoCollect module is under development to automatically deduce and set the optimal data collection parameters, while an AutoProcess module will evaluate the diffraction in real time to confirm the Laue symmetry and monitor radiation damage. We anticipate that these tools will increase experimental efficiency for both individual users and large-scale efforts alike.
Work was funded in part by the US Department of Energy under Contract No. DE-AC03-76SF00098, and by NIH/NIGMS under grant number 1P50GM62412.
2008 Run
Nov 19th - Dec 22nd
