Collaborative Science

Accelerating time to market and driving innovation with collaboration, knowledge based understanding and prediction.

Structure Based Design

Structure-Based Design (SBD) and the related Fragment-Based Design (FBD) are well established strategies in the rational development of small molecule drugs. Knowledge of how a small molecule binds into a protein affords considerable advantages, both in terms of prioritizing compounds for early stage screening, through to optimizing potency and selectivity. Discovery Studio delivers a comprehensive, scalable portfolio of scientific tools, tailored to support and assist SBD and FBD strategies from hit discovery through to late-stage lead optimization.

  • Prepare macromolecule structures for SBD
    • Analyze and prepare 3D structure models (e.g., PDB, X-ray structure, homology model) using MODELER
    • Predict residue ionization states at pH
    • Identify and study putative ligand binding sites
  • Prepare ligands
    • Clean up and calculate 3D coordinates
    • Generate ligand conformations
    • Filter ligands based on molecular properties, or undesirable groups
  • Hit Identification and optimization
    • Perform virtual screening on ligands and fragments using either the CATALYST pharmacophore engine, or the LIBDOCK or CDOCKER docking approaches
    • Identify critical interacting residues using the most comprehensive set of favourable, unfavourable and unsatisfied non-bond monitors on the market!
    • Profile and prioritize screening hits
    • Optimizing potency and target specificity
    • Score binding interactions with explicit solvent in situ MM-PBSA or MM-GBSA CHARMm-based methods
    • Accurately predict relative ligand binding energy for a congeneric ligand series using the new free energy perturbation (FEP) method
    • Perform in situ lead optimization using classical medicinal chemistry reaction transformations and commercially-available reagents
    • Scaffold-hop or perform R-group substitutions in situ using molecular fragments derived from commercially-available compounds
  • Extend the reach of your SBD project easily with additional design tools:
    • Perform combinatorial library design and optimization using Pareto optimization, diversity and similarity analysis
    • Calculate QSAR, fingerprint, and Quantum Mechanics based descriptors
    • Create advanced statistical models including Bayesian models, MLR (Multiple Linear Regression), PLS (Partial Least Squares), GFA (Genetic Functional Analysis), and NN (Neural Networks)
    • Build in drug-like and ADME properties
    • Minimize toxicity using TOPKAT
    • Optimize pharmacokinetic profile

Read the Discovery Studio Structure-Based Design Datasheet