AutoDock_doc_japanese_ver.1.0

This is a manual of AutoDock & AutoDockTools in Japanese. Autodock is a molecular docking simulation software.

AutoDock & AutoDockToolsに関する日本語マニュアルです。Autodockは、主にタンパク質-低分子化合物の複合体予測を行うソフトウェアです。

Transcript

1. 1 120704 ver. 1.0 Presented by Satoshi Kume, Osaka Pref. Univ. How to use AutoDock 4.2 on Mac 1. Auto Dock (http://autodock.scripps.edu/)ͱ MGL Tools (http://mgltools.scripps.edu/)Λμ ΢ϯϩʔυ͢Δɻ 2. MGL Tools ͷ AutoDock Tools Λىಈ͢Δɻ 3. Protein Data Bank(http://www.rcsb.org/pdb/home/home.do)ΑΓ PBD ϑΝΠϧΛऔಘ͢Δɻ 3. Protein ͱ Ligand ͷ PDB ϑΝΠϧ͔Β PDBQT ΁ม׵͢Δɻ PDBQT ϑΝΠϧ͸ɺݪࢠిՙͱ Torsion ͷఆٛΛ෇͚Ճ͑ͨ PDB ϑΝΠϧͰ͋Δɻ a. Process for Protein File → Read Molecule → Open PDB file (Check Ribon.) Edit → Hydrogens → add → Polar only → OK. Edit → Charges → Compute Gasteiger → OK (Edit → Hydrogens → Merge Non-Polar) (Edit → Atoms → Assign AD4 type) File → save → Write PDBQT (or Grid → Macromolecule → Choose ಉ͡ PDB file → Save PDBQT) Edit → Delete → All molecules b. Process for Ligand Ligand → input → open Ligand PDB File Ligand → Torsion Tree → Direct Root Ligand → Torsion Tree → Choose Torsions → Done Ligand → Output → save as PDBQT Edit → Delete → All molecules 4. Protein ͷ flexible residues Λઃఆ͢Δɻ Flexible Residues → Input → Open PDBQT file flexible ʹ͍ͨ͠ Amino acid residues ͷ Sel.(select)Λબ୒͢Δ(less than 32 residues)ɻ flexible Residues → Choose Torsions in Currently Selected → Residues → OK flexible Residues → Output → Save Flexible PDBQT or Save Rigid PDBQT Edit → Delete → All molecules
2. 2 5. GridBox Λઃఆ͢Δɻ Grid → Micromolecules → Open PBDQT file Grid → Set Map Types → Open ligand PDBQT file Grid → Grid Box → Grid Box ͷઃఆ → File → close saving current Grid → output → Save GPF 6. Run AUTOgrid ͢΂ͯಉ͡ File ಺Ͱߦ͏ɻ RUN → AUTOgrid4 Program Pathname → universal darwin10 ͷ AUTOgrid4 Λબ୒ Parameter Filename → gpf file Log Filename → glg file λʔϛφϧΛىಈ → bash Λىಈ͢Δ PDBQT ͷ͋Δ File ·ͰҠಈͯ͠ɺCMD ίʔυΛష෇͚ɺEnter Map file ͕Ͱ͖Δɻ Edit → Delete → All molecules 7. Docking ύϥϝʔλΛઃఆ͢Δɻ Docking → Macromolecules → Set Rigid Filename → PDBQT File of Protein Docking → Ligand → Open PDBQT File of ligand → Accept Docking → Search Parameters → Genetical Algoritm Parameters → Number of GA Runs ≥ 200, Maximum Number of generation: 270000 → Accept Docking → Docking Parameters → Accept Docking → Output → Lamarckian GA 8. RUN AUTODOCK4 RUN → RUN AUTODOCK4 Program Pathname → universal darwin10 ͷ AUTODOCK4 Λબ୒ Parameter Filename → dpf file Log Filename → dlg file λʔϛφϧΛىಈ → bash Λىಈ͢Δ PDBQT ͷ͋Δ File ·ͰҠಈͯ͠ɺCMD ίʔυΛష෇͚ɺEnter ΞΫςΟϏςΟϞχλͰ Autodock ͷಈ࡞Λ֬ೝɻ MGL Toolsɺٴͼ X11 ͸ফͯ͠΋େৎ෉ɻ
3. 3 9. Docking Data Analysis AutoDock Tools) Analyze → Docking → Open DLG file Open PDBQT file of Protein Analyze → Clustering → Show (Xterm → cd file → less DLG file → /Rank → /number / → control + Z) 10. Pymol Ͱͷ Docking ϑΝΠϧͷ࡞੒ ~ dlg ϑΝΠϧΛ pdb ϑΝΠϧ΁ม׵ ~ Terminal) cd docking file Terminal) grep '^DOCKED' ???.dlg | cut -c9- > ???.pdbqt Terminal) cut -c-66 ???.pdbqt > ???.pdb Terminal) less ???.dlg Pymol) File → Open PDB file of Ligand Docking Pymol) File → Open PDB file of Protein ௥ه 11. ϦΨϯυ pdb ϑΝΠϧͷ࡞੡ ᾇChemskech software ͰϦΨϯυͷԽֶߏ଄ࣜΛ࡞੡͢Δɻ Tools ˠ 3D …. File ˠ Export ˠ save .mol file Open .mol file by Chimera ˠ save as a pdb file ᾈ Pubchem ͷ SMILE ͔Β PDB file ͷ࡞੡ Pubchem ͰϦΨϯυͷ SMILE Λίϐʔͯ͠ɺCORINA demo ʹ Submit ͢Δɻ CORINA (http://www.molecular-networks.com/online_demos/corina_demo) ᾉ Pubchem ͷ sdf file ͔Β PDB file ͷ࡞੡ ϦΨϯυͷ sdf file Λμϯϩʔυͯ͠ɺChimera Ͱ pdb file ʹม׵͢Δɻ 12. Pubchem ͷ SMILE ͔Β logP ܭࢉ ALOGPS ʹϦΨϯυͷ SMILE Λϖʔετͯ͠ɺSubmit ͢ΔɻlogP ΍ pKa ͳͲ͕ܭࢉ͞ΕΔɻ http://www.vcclab.org/lab/alogps/