Autok-分子对接步骤

1、Discoverystudio:File-New-moleculewindow:出现如下窗口，将所要处理的分子*.sdf文件拖入,Chemistry-hydrogens-dele去掉所有氢，选中质子化的氮原子选中质子化的氮原子，Chemistry-charge:+1.Chemistry-hydrogens-add.（加上所有氢，包括质子化的氢原子）a12Pdbqt格式准备（pymol）:4M48-DAT.pdb用pymol读入：点右下方S键，在左上方显示序列，选中21B,右侧显示有sele后，file-savemolecular:sele-OK-重命名ligand.pdbFile-open-D

2、uloxetine_3d.sdfSavemolecular:Duloxetine-3d.pdb受体准备：1. Pymol软件：pymol打开两个蛋白分子的pdb格式，将SERT-model叠合至U4M48-DAT上，保存叠合后的SERT-model.pdb。（此步骤是重新定义SERT-model的坐标）2. AutoDockTools:file-ReadMolecule:SERT-moldel-align.pdbEdit-Hydrogens:polarOnly-OkGrid-Macromolecule-choose:SERT-moldel-align.保存为：SERT-moldel-align

3、.pdbqt配体准备：Ligand-input-open:（*.pdb）ligand.pdb|Duloxetine-3d.pdbLigand-Output-SaveasPDBQT:保存为*.PDBQT文件。找活性位点，计算格点：Grid-Macromolecule-open:SERT_model_align.pdbqt弹出对话框：NO、确定、确定Ligand-input-open:ligand.pdbqt弹出对话框：确定Grid-setmaptypes-chooseligand:ligandGrid-GridBox-center-centeronligand:存图片或outputgriddim

4、ensionsfile|closesavingcurrentLigand-input-open:Duloxetine_3d.pdbqt弹出对话框：确定Grid-Macromolecule-choose:SERT_model_align弹出对话框：NO、确定、确定Grid-setmaptypes-chooseligand:Duloxetine-3dGrid-output-saveGPF:SERT-Drug.gpfRun-AutoGridMacroNameHostName:nAutoGrrdwangpplDRBmacroswangpp-IDRB,/FkingDirectoryProgramPath

5、nameParameterFilenameLogFilename:D:wangpanpansvmdockingAutoDock-research|f/$aftware/AUTOdock/autogrid4exeBrowseBrowseBrowseBrowseMacromolecule-setrigidfilename:SERT-moldel-alignDocking-Ligand-choose:Duloxetine_3d弹出对话框：AcceptDocking-Output-GeneticAlgorithm(4.2)|LamarckianGA(4.2):SERT-Drug-dock.dpfRun

6、-AutoDock7RunAutoDoc举1MacroNamewangpp-IDRBmacrosHostName:目ngpp-IDRSWorkingDirectoryD:wangpanpansvmdockingAut口Duek-researchBrowseProgramPathname:|F:ware/AUTQdock/autoJockJ.BrowseParameterFilename:10:/wangpanpansvmjdocking/AutoDock-research/SERT-Drug-ddck.dpfBrowseLogFilename：0/wangpanpansvm/docking/A

7、utoDock-research/3ERT*Drug-dockdig日rows。AddOptionalFlagsCYes荷NoNiceLevel:20Cmd:|F/softwareWUTOdck/autodocking-open:*dlg(SERT-Drug-dock-GA.dlg|SERT-Drug-dock-lamarkianGA.dlg)Analyze-conformationsplay:可看各个构型。(Ligand-input-open:ligand.pdbqt两个相比，可以看到哪个构型与样本配体结构最相Ie3DGraphicsEditSelectDisplayColorComputeHydrogenBond