Multiple ligands in enzyme design application

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    • #1512

        Hello everyone,

        I am trying to use enzyme design application to predict favorable mutations for my research. I am only specifying a refile and no constraint file. The input pdb is what was predicted from the ligand dock application. I am working with a heme protein, so the input pdb has multiple ligands (heme and substrate). The ligand dock application worked great after keeping the substrate as the last entry in the pdb. However, the enzyme design application is giving error saying that it does not support multiple ligands. Since the documentation for enzyme design states that it is based on the ligand dock functionality, I am wondering if I am doing something wrong.

        Also, if it is indeed impossible to use the enzyme design application with multiple ligands, what other options do I have? Would rosetta scripts be useful for this?

        Thanks in advance!

      • #8396

          There is no a priori reason that the enzyme design protocol shouldn’t be able to support multiple ligands. The only possible problem would be in the autodetection of what the ligand is.

          What is the exact error message you are receiving? If I know this, I’ll be better able to look for a way around it.

          The other possibility is to use the RosettaScripts interface to the enzyme design functionality, rather than the enzyme_design application. This would allow for direct specification of the ligand, and would avoid the issues with autodetection.

        • #8399

            Thanks for the quick response! These are the last few lines of output-
            WARNING: the input pose has more than two chains, interface score reported in scorefile might not be accurate.
            WARNING: the input pose has more than two chains, interface score reported in scorefile might not be accurate.
   Database file opened: scoring/score_functions/SurfacePotential/average_hASA_by_res_and_neighbor.txt
   Database file opened: scoring/score_functions/SurfacePotential/surface_score.txt
   Database file opened: scoring/score_functions/SurfacePotential/hpatch_score.txt

            ERROR: Pose has more or less than one ligand. This mover atm can only hadndle poses with one ligand.
            ERROR:: Exit from: src/protocols/enzdes/ line: 369

            Additional info: Three chains are A-protein, B-heme, and C-substrate. The file was the output of ligand_dock application and has not been modified.

            Also, I am currently looking into rosetta scripts. Thanks for the input.

          • #8404

              That message is probably occurring because you’re using the -final_repack_without_ligand option. When Rosetta goes to remove the ligand, it sees that you have two of them and then doesn’t know what to do with them. Try removing that flag from your runs. (Note that the RepackWithoutLigand filter in RosettaScripts unfortunately will also have this issue.)

            • #8405

                That did the trick! Thanks so much. Now I only get the warning messages but the program doesn’t quit.

                One thing I found interesting was that if the option -out:file:o is not present, it still runs the code without exiting even when the -final_repack_without_ligand option is present. However, the score fields starting with ‘SR’ are not present in output PDBs.

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