Rapid-Response Crystallography

Technology Operations Core 1: Abstract
Technology Operations Core 1 (TOC1) of the ALS-ENABLE resource supports the rapid response to
macromolecular crystallography diffraction data collection. It joins forces, and groups together the effort and
expertise of three world-leading groups operating macromolecular crystallography beamlines at the ALS. They
are the Berkeley Center for Structural Biology (BCSB), the Molecular Biology Consortium (MBC) and the
University of California at San Francisco. The ALS-ENABLE facility includes eight macromolecular
crystallography beamlines with a broad range of capabilities to address all structural biology projects. NIH
investigators can request beamtime and, following a positive review, will get beamline access within a month.
Three modes of access are made available to users under the rapid response in TOC1. The vast majority of
users take advantage of the remote access capabilities available at all beamlines. Users ship their samples
and the ALS-ENABLE staff will prepare the beamline and load users’ samples in the robotic system. The
investigators will then operate the beamline from their home or institution for the acquisition of diffraction data.
A new mode of access proposed in this effort is to use the fully automated data collection pipeline. Here,
diffraction data are acquired automatically without manual intervention. This has been exploited heavily in
fragment-based drug discovery campaigns in the fight against COVID-19 pandemic. The automated data
collection pipeline has shown to be powerful and acquire diffraction datasets on crystals that appears to be
unusable. Users can also rely on the collaborative crystallography programs. More often novice structural
biologists will need help in their effort to determine the structure of biological molecules. Collaborative
crystallography relies on expert scientists available from the ALS-ENABLE staff to collect diffraction data on
their behalf. The range of provided expertise can start with guidance with crystallization up to publication of the
results. The collaborative crystallography program will also support the automated data collection pipeline by
identifying challenging projects that may need manual intervention. This will ensure that users are getting the
best diffraction data from their precious samples. Altogether TOC1 intends to quickly respond to the need of
macromolecular crystallography NIH investigators for access to diffraction data at the ALS.

Grant Number: 5P30GM124169-09
NIH Institute/Center: NIH
Principal Investigator: MARC ALLAIRE