Computer-Aided Molecular Modeling (CAMM)

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????????????????????????
????????? Computer-Aided Molecular Modeling
(CAMM) Research Center Kansai ?? ??
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??
?????
?? ?????????????(????)???????????
??????????????????????????????
????????????
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???????????????????
Virtual Screening 3D-???????????? -
??????????????????? - ??????????????????????????
??????? - DOCK, FlexX, Ludi, ICM
Docking Simulation ??????? -
?????????????????????????? - ???????????????????
?????? - AutoDock, GOLD
Binding Energy/Mode Prediction ???????ｷ???? -
??????????????????????? - ?????????? -
1?????????????? - FEP(Free Energy
Perturbation)??LIE(Linear Interaction Energy)?
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??? ??
Estrogen receptor???????????(OHT)?X???????????????
???????????????????
- Estrogen receptor ??????????
???(??)??????????? - Tamoxifen(Aventis)
??????????
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??? ??
Virtual Screening Tool DOCK4.0 3D DB
ｷ??????????? ?????
(Maybridge?SALOR?) ｷCORINA2.6?3D????
ｷ?36?3D?????????
???????????? 1000???
Docking Simulation Tool AutoDock3.0
HW SGI O2 R5000 (180MHz)
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??? DOCK

1. sphere?????????????????

DOCK Kuntz(UCSF)?????????3D-DB????Tool

• ??
• ?????????sphere(??????)????????????????????docking
  ?????????

1. docking???????grid????????????????????????????????
   ?????

?? - ??????? - ??????????????? - sphere?????
- grid?????????????
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??? AutoDock

1. ?????????????????????GA?????????????????

AutoDock Morris Olson(Scripps)?????????docking?T
ool

• ??
• docking???????grid????????????????????????????????
  ?????

1. ??????????????????grid????????????????????????????
   ????

?? - ??????????? - ???????????????? -
grid????????????? - ????????
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??? ??(DOCK virtual screening)
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??? ??(AutoDock docking simulation)
AutoDock Top10 from 2nd DOCK with OHT? LGA (10
runs)
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??? ??

• Estrogen receptor??????????DOCK?AutoDock??????????
  3D???????????????estrogen receptor????????????????
  ????
• ???X??????????????????????????
• ??????????????????????????????????????????????????
  ?????????????????

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????????
Structure-based chemical knockout -
?????????????????????????? - ??????????? Ligand
finding for orphan receptors -
?????????????????????????? - ???????????????????
?? Protein-protein association analysis -
???associate?????? - ?????????