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ligand_docking: ligand preparation

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ligand_docking: ligand preparation

I am doing ligand docking and have a general questions regarding ligand preparation. I used tutorial described here to develop a protocol It works very well when I dock the native ligand downloaded together with the crystal structure back to the protein scaffold. Since I will dock unnatural ligand into this protein fold later, I tried to test my overall procedure by draw the native ligand and minimize its energy by using obabel. However, I am not able to get the manually generated ligand docked back to the original location (as attached in the figure, the orange one is docked, and red on is the original crystal structure). I am wondering how can I improve this situation. the docking script I used like below: 

Thank you very much 


                        <ScoreFunction name="ref2015_soft" weights="ref2015_soft.wts">


                        <ScoreFunction name="ref2015" weights="ref2015.wts">





                        <LigandArea name="inhibitor_dock_sc" chain="X" cutoff="5.0" add_nbr_radius="true" all_atom_mode="false"/>

                        <LigandArea name="inhibitor_final_sc" chain="X" cutoff="5.0" add_nbr_radius="true" all_atom_mode="false"/>

                        <LigandArea name="inhibitor_final_bb" chain="X" cutoff="6.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>




                        <InterfaceBuilder name="side_chain_for_docking" ligand_areas="inhibitor_dock_sc"/>

                        <InterfaceBuilder name="side_chain_for_final" ligand_areas="inhibitor_final_sc"/>

                        <InterfaceBuilder name="backbone" ligand_areas="inhibitor_final_bb" extension_window="3"/>




                        <MoveMapBuilder name="docking" sc_interface="side_chain_for_docking" minimize_water="false"/>

                        <MoveMapBuilder name="final" sc_interface="side_chain_for_final" bb_interface="backbone" minimize_water="false"/>



                <SCORINGGRIDS ligand_chain="X" width="20">

                        <ClassicGrid grid_name="classic" weight="1.0"/>




                        <Transform name="transform" chain="X" box_size="7.0" move_distance="0.2" angle="20" cycles="500" repeats="1" temperature="5"/>

                        <HighResDocker name="high_res_docker" cycles="6" repack_every_Nth="3" scorefxn="ref2015_soft" movemap_builder="docking"/>

                        <FinalMinimizer name="final" scorefxn="ref2015" movemap_builder="final"/>

                        <InterfaceScoreCalculator name="add_scores" chains="X" scorefxn="ref2015" native="3TX9.A_FMN_Crystal.pdb"/>




                        <Add mover_name="transform"/>

                        <Add mover_name="high_res_docker"/>

                        <Add mover_name="final"/>

                        <Add mover_name="add_scores"/>


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Thu, 2020-05-21 09:42