The HZB F2X-facility -- an efficient crystallographic fragment screening
platform
Abstract
Crystallographic fragment screening (CFS) has recently matured into an
important method for the early stages of drug discovery projects. It is
based on high-throughput structure determination and thus requires a
high degree of automation as well as specialized workflows and robust
analysis tools. Consequently, large-scale research facilities such as
synchrotrons have embraced the method, and developed platforms to
perform CFS campaigns with the help of crystallography experts and
specific tools. The BESSY II synchrotron, operated by the
Helmholtz-Zentrum Berlin (HZB), is one of these synchrotron facilities
that offer a CFS platform, named the F2X-facility. Here, the specialized
F2X workflow is described along with the relevant differences to other
existing CFS platforms, and the ongoing developments aimed at supporting
users of the facility. The different stages of a CFS campaign including
requirements, beamline capabilities, and the software environment are
detailed and explained. A unique F2X-GO kit is featured, which allows
users the possibility of performing all sample preparation in their home
laboratories. Furthermore, at the HZB a computational workflow has been
built to support users beyond the hit identification stage. The
advantages of the F2X-facility at HZB are described and references are
provided to successfully conduct CFS.