Hello,
I am performing Rosetta ligand docking for an enzyme A to a ligand X which should be covalently bound to a small protein B. I need to impose this covalent bond and some other catalytic constraints (distances between ligand and receptor's residues and also the distances between two residues of the receptors ) to my ligand docking. I found several movers for adding constraints including AddorRemoveMatchCsts, Addconstraints Mover, and ConstraintSetMover, but I am confused about which one works with Rosetta Ligand docking.
I have studied Rosetta documentation and I saw "AddorRemoveMatchCsts" is used in EnzymeDesign protocol. I was thinking to add "AddorRemoveMatchCsts" to ligand docking movers since it allows me to define the covalent bond. In other words, the protocols would be like below.
Moreover, I was wondering whether I need to generate more 100 conformers for my ligand since it is large (it has 25 rotatable bonds).
I really appreciate it if you could help me in this regard.
<MOVERS>
<AddOrRemoveMatchCsts name="cstadd" cst_instruction="add_new"/>
<Transform name="transform" chain="X" box_size="10.0" move_distance="0.25" angle="20" cycles="500" repeats="1" temperature="5" initial_perturb="5"/>
<HighResDocker name="high_res_docker" cycles="6" repack_every_Nth="3" scorefxn="ligand_soft_rep" movemap_builder="docking"/>
<FinalMinimizer name="final" scorefxn="hard_rep" movemap_builder="final"/>
<InterfaceScoreCalculator name="add_scores" chains="X" scorefxn="hard_rep"/>
<ConstraintSetMover name="refinement_constraint" add_constraints="True" cst_file="../input_files/refinement_constraint.cst"/>
<StartFrom name="mystart" chain="X" use_nbr="true" >
<Coordinates x="20.037" y="35.45" z="74.245"/>
</StartFrom>
</MOVERS
<PROTOCOLS>
<Add mover_name="cstadd"/>
<Add mover_name="mystart"/>
<Add mover_name="transform"/>
Add mover="refinement_constraint" />
<Add mover_name="high_res_docker"/>
<Add mover_name="final"/>
<Add filter="ACP_connection"/>
<Add filter="D281"/>
<Add filter="E319"/>
<Add filter="hb_D281_H285"/>
<Add filter="hb_D281_N283"/>
<Add mover_name="add_scores"/>
</PROTOCOLS>