model_aliganed蛋白与NTBC、HPPA、sulco、mesot小分子结合体对接：error not exist 00B

最新推荐文章于 2024-05-03 05:42:08 发布

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最新推荐文章于 2024-05-03 05:42:08 发布

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1、
（1）生成小分子NTBC的conformers文件

D:\bcl_4.0>bcl.exe molecule:ConformerGenerator -ensemble_filenames NTBC.sdf -conformers_single_file NTBC.conformers.sdf

（2）生成小分子sulcotrione的conformers文件

D:\bcl_4.0>bcl.exe molecule:ConformerGenerator -ensemble_filenames sulcotrione.sdf -conformers_single_file sulcotrione.conformers.sdf

（3）生成小分子mesotrione的conformers文件

D:\bcl_4.0>bcl.exe molecule:ConformerGenerator -ensemble_filenames mesotrione.sdf -conformers_single_file mesotrione.conformers.sdf

2、
（1）cat生成make_params.NTBC.sdf、mesotrione、sulcotrione

unbuntu@unbuntu-virtual-machine:~/ligand_docking/3_Ensemble_docking$ cat prep/aligned_ligands/NTBC.sdf prep/conformers/NTBC.conformers.sdf >> prep/make_params/make_params.NTBC.sdf

unbuntu@unbuntu-virtual-machine:~/ligand_docking/3_Ensemble_docking$ cat prep/aligned_ligands/mesotrione.sdf prep/conformers/mesotrione.conformers.sdf >> prep/make_params/make_params.mesotrione.sdf

unbuntu@unbuntu-virtual-machine:~/ligand_docking/3_Ensemble_docking$ cat prep/aligned_ligands/sulcotrione.sdf prep/conformers/sulcotrione.conformers.sdf >> prep/make_params/make_params.sulcotrione.sdf

（2）一个小分子使用一个链，生成00B.00C、00D、00E.pdb(结合为一个文件作为对接的小分子)、00B_conformers.sdf、00B.params、00C、00D、00E
保存到/home/unbuntu/ligand_docking/3_Ensemble_docking/prep/rosetta_inputs/
不然会报错

HPPA小分子

unbuntu@unbuntu-virtual-machine:~/ligand_docking/3_Ensemble_docking$ /home/unbuntu/rosetta_src_2019.35.60890_bundle/main/source/scripts/python/public/molfile_to_params.py prep/make_params/make_params.HPPA.sdf --chain B -n 00B -p 00B --conformers-in-one-file

NTB小分子

unbuntu@unbuntu-virtual-machine:~/ligand_docking/3_Ensemble_docking$ /home/unbuntu/rosetta_src_2019.35.60890_bundle/main/source/scripts/python/public/molfile_to_params.py prep/make_params/make_params.NTBC.sdf --chain C -n 00C -p 00C --conformers-in-one-file

mesotrione小分子

unbuntu@unbuntu-virtual-machine:~/ligand_docking/3_Ensemble_docking$ /home/unbuntu/rosetta_src_2019.35.60890_bundle/main/source/scripts/python/public/molfile_to_params.py prep/make_params/make_params.mesotrione.sdf --chain D -n 00D -p 00D --conformers-in-one-file

sulcotrione小分子

unbuntu@unbuntu-virtual-machine:~/ligand_docking/3_Ensemble_docking$ /home/unbuntu/rosetta_src_2019.35.60890_bundle/main/source/scripts/python/public/molfile_to_params.py prep/make_params/make_params.sulcotrione.sdf --chain E -n 00E -p 00E --conformers-in-one-file

3、将上一步生成的四个00B文件复制粘贴为一个文件命名为HPPALigand.pdb
放入/home/unbuntu/ligand_docking/3_Ensemble_docking/inputs/

4、在option中

-in
 -file
  -s "inputs/model1_aligned.pdb inputs/HPPALigand.pdb"
  #model1_aligned.pdb为模拟工作得到的蛋白质：5cto蛋白与RCSB pdb网站发来的pdb结合后的蛋白质

5、把dock.xml添加bcde链

<ROSETTASCRIPTS>Dock the ensemble of ligand into the native structure using the Rosetta Score based affinities 

	<SCOREFXNS>
		<ScoreFunction name="ligand_soft_rep" weights="ligand_soft_rep">
			<Reweight scoretype="fa_elec" weight="0.42"/>
			<Reweight scoretype="hbond_bb_sc" weight="1.3"/>
			<Reweight scoretype="hbond_sc" weight="1.3"/>
			<Reweight scoretype="rama" weight="0.2"/>
		</ScoreFunction>
		<ScoreFunction name="hard_rep" weights="ligand">
			<Reweight scoretype="fa_intra_rep" weight="0.004"/>
			<Reweight scoretype="fa_elec" weight="0.42"/>
			<Reweight scoretype="hbond_bb_sc" weight="1.3"/>
			<Reweight scoretype="hbond_sc" weight="1.3"/>
			<Reweight scoretype="rama" weight="0.2"/>
		</ScoreFunction>
	</SCOREFXNS>
	<LIGAND_AREAS>
	Docking_Sidechains

<LigandArea name="dock_sc_B" chain="B" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>
<LigandArea name="dock_sc_E" chain="E" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>
<LigandArea name="dock_sc_D" chain="D" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>
<LigandArea name="dock_sc_C" chain="C" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>

  Final_Sidechains

<LigandArea name="final_sc_B" chain="B" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>
<LigandArea name="final_sc_E" chain="E" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>
<LigandArea name="final_sc_D" chain="D" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>
<LigandArea name="final_sc_C" chain="C" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>

	Final_Backbones	

<LigandArea name="final_bb_B" chain="B" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>
<LigandArea name="final_bb_E" chain="E" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>
<LigandArea name="final_bb_D" chain="D" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>
<LigandArea name="final_bb_C" chain="C" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>

	</LIGAND_AREAS>
	<INTERFACE_BUILDERS>
		<InterfaceBuilder name="side_chain_for_docking" ligand_areas="dock_sc_B"/>
		<InterfaceBuilder name="side_chain_for_final" ligand_areas="final_sc_B"/>
		<InterfaceBuilder name="backbone" ligand_areas="final_bb_B" extension_window="3"/>
	</INTERFACE_BUILDERS>
	<MOVEMAP_BUILDERS>
		<MoveMapBuilder name="docking" sc_interface="side_chain_for_docking" minimize_water="true"/>
		<MoveMapBuilder name="final" sc_interface="side_chain_for_final" bb_interface="backbone" minimize_water="true"/>
	</MOVEMAP_BUILDERS>

Grid will be formed using the included chain so set ligand_chain to A, the protein chain 
	<SCORINGGRIDS ligand_chain="A" width="15">
		<ClassicGrid grid_name="classic" weight="1.0" atr="-1.0" rep="0.5" />
		</SCORINGGRIDS>

	<MOVERS>
              <StartFrom name="start_from" chain="B,C,D,E">
		     <Coordinates x="28.349" y="-21.302" z="4.107"/>
	      </StartFrom>
		<TransformEnsemble name="transform_ensemble" chains="B,C,D,E" box_size="50" move_distance="0.2" angle="20" cycles="1000" repeats="1" temperature="5" initial_perturb="5.0" use_conformers="true" optimize_until_score_is_negative="true" />
		<HighResEnsemble name="high_res_ensemble" chains="B,C,D,E" cycles="9" repack_every_Nth="3" scorefxn="ligand_soft_rep" movemap_builder="docking" rosetta="false" final_score="hard_rep" final_move="final"/>
	
 </MOVERS>
 <PROTOCOLS>
     <Add mover_name="start_from"/>
	 <Add mover_name="transform_ensemble"/>
	 <Add mover_name="high_res_ensemble"/>
 </PROTOCOLS>
</ROSETTASCRIPTS>

6、对接

unbuntu@unbuntu-virtual-machine:~/ligand_docking/3_Ensemble_docking$ /home/unbuntu/rosetta_src_2019.35.60890_bundle/main/source/bin/rosetta_scripts.linuxgccrelease @inputs/options -docking:ligand:ligand_ensemble 0 -nstruct 10 -qsar:grid_dir fold_name

File: src/core/chemical/ResidueType.cc:2718
AFFINITY does not exist in ResidueType with name 00B