Does it make sense to perform Docking on a complex?

[Anonymous]

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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