Applying New Protocol to Kinase Inhibitors: Pilot Study

• Panel of 4 kinase active sites

  • General kinase features & specificity pockets defined (co-crystal structures)

• DockIt with 300k pre-filtered commercially available compounds

  • Physical chemical properties
  • Undesirable substructures
  • HB donor and acceptor present

• Apply Magnet filter for general kinase features before saving DockIt output

  • Relaxed HB definitions to allow following minimization to adjust positioning

• Run Magnet (relaxed HB definitions) on output & select poses: general kinase features and target specific features

• Minimize selected poses in Flo+

• Rerun Magnet with regular HB definitions & select poses

• Order 25k compounds (ChemNavigator)

• Throughput on Linux cluster with 51 CPUs, 4 active sites 100 poses/compound => 44’/1k compounds, 33k/day 250 poses/compound => 93’/1k compounds, 15k/day

Notes: