PanDDA analysis of DCP2B screened against DSPL/DSi Poised, OxXChem fragment libraries and initial follow up chemistry

SGC Oxford has performed a crystallographic fragment screen, and initial follow up chemistry on the Human m7GpppN-mRNA Hydrolase (DCP2/NUDT20, UniProtKB - QIU60). All structures with clearly identifiable ligands were deposited in the Protein Data Bank under Group Deposition ID G_1002061, the corresponding apo structures are deposited under Group Deposition ID G_1002062.

Experiment

Crystals were prepared at the XChem facility of the Diamond Light Source (DLS). Briefly, crystals were soaked overnight with two fragment libraries; the Diamond- SGC Poised Library set (Cox et al., 2016) and the OxXChem set with nominal fragment concentrations of 100 mM, with DMSO at 20% v/v. Additionally, a series of follow-up compounds based on an initial fragment hit was synthesized and soaked overnight with nominal compound concentrations of 10-200 mM, with DMSO at 20% v/v. All datasets were collected at MX beamlines at DLS. Autoprocessed datasets were analysed by Pan-Dataset Density Analysis (PanDDA) (Pearce et al., 2017). All ligands that were clearly identifiable in PanDDA event maps were modelled, refined and deposited into the PDB.

Content

This repository contains:

Modelled Data

• Organised by crystal identifier, each folder contains:
  • Autoprocessing data from Diamond Light Source automated pipelines (including MTZ)
  • PDB, CIF & PNG files of all the soaked compounds
  • PanDDA event maps
  • Final refine.pdb and refine.mtz files of all ligand bound structure
    • Superposed structures (refine.pdb)
    • Separated bound & ground states (refine.split.bound.pdb & refine.split.ground.pdb)

PanDDA Analysis Data

• This is split into two directories. This split is only due to technical limitations at the time of preparation of the data, and the timeliness of the data.
  • All results from the PanDDA analysis, including ground-state-mean maps and PanDDA event & Z-maps for all ligand bound structures.