Ulrike Uhrig
Computational Chemistry

Computational chemistry methods are integral to the process of active molecule identification and optimisation. These include:

  • Chemoinformatics approaches
  • Molecular modelling
  • Computational screening using ligand-based and structure-based design strategies
  • Managing compound acquisition through our chemistry partners
  • Commercial software available: SYBYL-X including SurflexDock and SurflexSim, LeadIT including FlexX and FlexS, Muse, Spartan
  • Access to the HPC compute cluster at EMBL which provides access to more than 5800 CPUs for scientific computing at EMBL

Structural biology

  • Protein structure visualisation (3D visualisation capabilities)
  • Binding site identification
  • Analysis of interaction profiles of ligands inside a binding site
  • Homology modeling; leveraging known protein structures to unknowns with similar sequence

Ligand-based design

  • Pharmacophore elucidation based on known active ligands
  • Database searching for new active compounds based on pharmacophore
  • Properties prediction based on models from data of known ligands
  • SAR, ADME predictions based on data from known ligands

Receptor-based design

  • Docking of ligands into target structure
    • Virtual screening; selection of compounds from large data set based on docking
    • Ligand refinement based on docked structure
  • De novo design of ligands from protein structure; no lead compound; spatial arrangement of suitable binding groups

Library design

  • Diversity and similarity tools
  • Library creation
    • For random screening
    • For specific targets
    • Exploration of SAR (iterative)

Data analysis approaches

Data analysis

  • Analysis of screening data; clustering hit compounds and prioritisation for follow-up investigations

Compound acquisitions

  • Identifying vendors and availability of desired compounds
  • Quote requests