The question about FavorNativeResidue

[Anonymous]

 I  read the paper Rosetta and the Design of Ligand Binding Sites doi:10.1007/978-1-4939-3569-7_4.

 

then try to use  EnzRepackMinimize  to design the protein.

But FavorNativeResidue was set as 0.5-3.0, the mutant position numbers are same and there are too many mutant positions.

However, I use the PackRotamersMover  by changing  FavorNativeResidue and can get different mutant position numbers.

How can I solve it? Thanks.

 

The design part  was set  as https://pubs.acs.org/doi/abs/10.1021/jacs.5b06622

      <MOVERS>

              <EnzRepackMinimize name=”desmin” design=”1″ repack_only=”0″ scorefxn_minimize=”myscore” scorefxn_repack=”soft_rep” minimize_rb=”1″ minimize_sc=”1″ minimize_bb=”0″ cycles=”1″ minimize_lig=”0″ min_in_stages=”0″ backrub=”0″ task_operations=”init,edto,resfile_design,limchi2,linmem_ig” />

              <EnzRepackMinimize name=”fin_min” repack_only=”0″ design=”0″ scorefxn_minimize=”myscore” scorefxn_repack=”myscore” minimize_rb=”1″ minimize_sc=”1″ minimize_bb=”1″ cycles=”1″ task_operations=”init,edto_repack,resfile_repack,limchi2,linmem_ig”/> 

              <EnzRepackMinimize name=”fin_rpkmin” repack_only=”1″ design=”0″ scorefxn_minimize=”myscore” scorefxn_repack=”myscore” minimize_rb=”1″ minimize_sc=”1″ minimize_bb=”0″ cycles=”1″ task_operations=”init,edto_repack,resfile_repack,limchi2,linmem_ig”/> 

              <GenericMonteCarlo name=”multides” mover_name=”desmin” filter_name=”interfE” trials=”4″ sample_type=”low” temperature=”0.6″ drift=”1″/> 

              <FavorNativeResidue name=”fnr” bonus=”1.5″/> 

      </MOVERS>

 

      <PROTOCOLS>

              <Add mover_name=”fnr”/>

              <Add mover_name=”multides”/>

              <Add mover_name=”fin_min”/>

              <Add mover_name=”fin_rpkmin”/>

      </PROTOCOLS>

[Anonymous]

I’m not certain, but my initial thought would be that the scorefunction you used doesn’t have the `res_type_constraint` turned on. The FavorNativeResidue mover adds the constraints to the pose, but for the constraints to actually be obeyed during the design run, you have to have the respective score term turned on in the scorefunction being used. Be sure to add that term to the scorefunctions being used.

The other possibility might be that EnzRepackMinimize is removing the constraints from the pose. You can check this by adding the CstInfoMover to the protocol after the EnzRepackMinimize mover and doing a short test run. (https://www.rosettacommons.org/docs/latest/scripting_documentation/RosettaScripts/Movers/movers_pages/CstInfoMover) the CstInfoMover should print out what constraints are active in the pose at the time of application, so you can see if the Residue type constraints for the native sequence are still active.

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