BioinformaticsofTCM-BIDD-NationalUniversityofSingapore.pptVIP

Systems: the way for TCM to produce clinical effects Fact1: Weak effect of components Fact2: Validated effect of TCM by clinical practice Inference: Interaction among components Targeting systems: interpreting the mechanism of TCM function Targeting systems: bridging biology and TCM theory Targeting systems: providing new cues for the treatment of complex disease Targeting systems: providing new resource for drug development A Proposed Platform for System-targeting TCM research Biological Systems related with TCM Prescriptions that Promoting Blood Circulation and Removing Blood Stasis What bioinformatics can do in TCM General Protein–Ligand Binding Ligand - Molecule that binds with a protein - DNA, drug lead compounds, etc. Protein active site(s) - Allosteric binding - Competitive binding Function of binding interaction - Natural and artificial . . . . Scoring in Ligand-Protein Docking Potential Energy Description: * * * * * * * Design of HIV-1 Protease Inhibitor Design of HIV-1 Protease Inhibitor Design of HIV-1 Protease Inhibitor 136 200 168 490 52 AH 3.34 0.40 0.001 33718 215 177981 HMG-CoA 3.14 0.49 0.002 40722 278 177981 5-HT3 3.35 0.54 0.002 31297 285 177981 PDE4 3.33 1.00 0.003 49172 532 177981 AngII 16.02 0.79 5E-04 6563 88 177981 ACE E AH/H A/D H A D D：number of molecules in database A：number of active molecules in database H：number of hit molecules AH：number of active molecules in hitlist Virtual Screening HMG -CoA T-cell PDE TNFɑ COX2 AngII INVDOCK Strategy for Match Making Science 1992;257: 1078 Proteins 1999; 36:1 INVDOCK Test on Targets of Chinese Medicinal Herbal Ingredients(Am. J. Chin. Med. 2002, 30, 139) Chinese Natural Product ? Number of Identified Putative and Known Therapeutic Targets Number Confirmed or Implicated Therapeutic Targets by experiment Number of Identified Putative and Known Toxicity/Side effect Targets Number Confirmed or Implicated Toxicity/Side Effect Targets by experiment Acronycine 3 1 4 - Allicin 5 2