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February 17, 2020 at 5:12 pm #3349Anonymous
I am trying to design an orthogonal ligand/receptor system. I’ve inherited the script below as a starting point but I’m wondering what exactly the Docking mover would be doing. My PDB structure is a ligand that is already bound to the binding domains on the receptor. Does it still make sense to perform a docking step in this scenario?
My script:
<ROSETTASCRIPTS>
<TASKOPERATIONS> You can control which parts you want to change from here
ProteinInterfaceDesign name="pido" repack_chain1="1" repack_chain2="1" design_chain1="1" design_chain2="0" interface_distance_cutoff="10"/> task operation that designates which residues are designable and repackable at the interface
</TASKOPERATIONS>
<FILTERS> This part enables to output useful values for post-processing
<Ddg name="ddG" scorefxn="talaris2014" threshold="-15" repeats="2"/> binding energy calculation; an average of two repeats is computed for better numerical accuracy
<Sasa name="sasa" threshold="100"/> Buried surface area upon complex formation
<Rmsd name="rmsd" confidence="0"/> confidence=0 means that the filter will be evaluated but not used as an acceptance criterion
<CompoundStatement name="ddg_sasa"> combine filters into a single logical statement
<AND filter_name="ddG"/>
<AND filter_name="sasa"/>
</CompoundStatement>
</FILTERS>
<MOVERS>
<Docking name="docking" score_high="soft_rep" fullatom="1" local_refine="1"/> Invokes RosettaDock local-refinement (in full-atom) with a soft potential
<BackrubDD name="backrub" partner1="0" partner2="1" interface_distance_cutoff="8.0" moves="1000" sc_move_probability="0.25" scorefxn="talaris2014" small_move_probability="0.15" bbg_move_probability="0.25"/> perturb the backbone of chain2. Change moves to 1000 for real application
<RepackMinimize name="des1" scorefxn_repack="soft_rep" scorefxn_minimize="soft_rep" minimize_bb="0" minimize_rb="1"/>
<RepackMinimize name="des2" scorefxn_repack="talaris2014" scorefxn_minimize="talaris2014" minimize_bb="0" minimize_rb="1"/> Design and minimization at the interface
<RepackMinimize name="des3" minimize_bb="1"/>
<ParsedProtocol name="design">
<Add mover_name="des1"/>
<Add mover_name="des2"/>
<Add mover_name="des3"/>
<Add mover_name="backrub"/>
<Add mover_name="des3" filter_name="ddg_sasa"/>
</ParsedProtocol>
<GenericMonteCarlo name="iterate" scorefxn_name="talaris2014" mover_name="design" trials="5"/> Iterate through design to find best solution. change trial numbers to higher for real application.
</MOVERS>
<PROTOCOLS>
<Add mover="docking"/>
<Add mover="iterate"/>
<Add filter="ddG"/>
<Add filter="sasa"/>
<Add filter="rmsd"/>
</PROTOCOLS>
</ROSETTASCRIPTS>
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