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

Data analysis

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