workflow-tools-for-crystallographic-fragment-screening-at-helmholtz

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin

Fragment screening is a technique that helps to identify promising starting points for ligand design. Given that crystals of the target protein are ...

Helmholtz-Zentrum Berlin

Freie Universität Berlin

Crystallographic fragment screening (CFS) provides excellent starting points for projects concerned with drug discovery or biochemical tool compound development. One of the fundamental prerequisites for effective CFS is the availability of a versatile fragment library. Here, we report on the assembly of the 1,103-compound F2X-Universal Library and its 96-compound sub-selection, the F2X-Entry Screen. Both represent the available fragment chemistry and are highly diverse in terms of their 3D-pharmacophore variations. Validation of the F2X-Entry Screen in CFS campaigns using endothiapepsin and the Aar2/RNaseH complex yielded hit rates of 30% and 21%, respectively, and revealed versatile binding sites. Dry presentation of the libraries allows CFS campaigns to be carried out with or without the co-solvent DMSO present. Most of the hits in our validation campaigns could be reproduced also in the absence of DMSO. Consequently, CFS can be carried out more efficiently and for a wider range of conditions and targets.

Tatjana Barthel

Macromolecular Crystallography

Helmholtz-Zentrum Berlin

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin

Tatjana Barthel

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Macromolecular Crystallography

Helmholtz-Zentrum Berlin

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin

Macromolecular Crystallography