Virtual Screening

1
Virtual Screening

• protein-ligand interactions, inhibitors, SBDD
• kinetics, competitive, slow, aggregators
• H-bonding, halogens, co-factors, metal ions
• chemi-informatics
• tanimoto similarity, clustering
• Lipinskis rules
• predicting solubility, aggregation
• 3D conformational sampling (but not rings) ROCS
• pharmacophore search
• QSAR, GRID
• screening
• docking algorithms, scoring functions

2

• screening
• docking algs anchor-and-grow, ICM, Monte Carlo
• receptor flexibility (dof, MD)
• partial charges, tautomers
• solvation energy
• entropy
• mining minima (Gilson and Zhou, 2007)
• -0.4..-1 kcal/mol/rotbond
• LUDI/Chemscore
• PMF
• consensus scoring, LIE

3
Induced Fit

• James and Tawfik (PNAS, 2005)
• IgE antibody binds many ligands promiscuously,
  but only a few specifically and tightly
• anthrone (2BJM) vs. alizarin red (1OAR)
• involves secondary isomerization, movement of Tyr
  in H3 loop by 14A to grasp ligand tighter
• multiple phases/rates in pre-steady state kinetics