Virtual Screening protein-ligand interactions, inhibitors, SBDD –kinetics, competitive, slow, aggregators –H-bonding, halogens, co-factors, metal ions.

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Presentation transcript:

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

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) kcal/mol/rotbond –LUDI/Chemscore –PMF –consensus scoring, LIE

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