ratio of conformers and docking output

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    • #2099


        I am performing docking claculations using RosettaLigand. I have two questions regarding RosettaLigand docking:

        1. How does Rosetta ligand process the ligand conformers fed to dock a structure? I mean does it try all the ligand conformers sequentially in the input file or does it pick them randomly, if so on what criteria?

        2. what is the basis for conformer being retained with model and produced as output: that is as a docked pose? is there any ratio (between the input ligand conformers and the ouput docked structures from each homology model in a docking run) that as to be followed depending on the conformers fed as input file to obtain the output docked poses, so that efficient sampling is done.


      • #10696

          The ligand conformers in the docking process are treated almost identically to the sidechain conformers. What happens is that when Rosetta attempts to find the conformation of the sidechains (“packing”), it also attempts to find the ligand conformation. This happens with a Monte-Carlo simulated annealing process (based on total energy of the pose) so it’s accurate to say that the conformers are tried randomly, but the settings are such that all of the conformers will be attempted in the course of a single packing run (of which there are many during the run of a single ligand docking output structure). There’s also steps where the ligand conformations are tried sequentially (“rotamer trials”) by putting them into the structure and evaluating the energy in the current context – then only the lowest energy conformer is then taken forward.

          Conformers make it to the output structure based on their energy during the docking process. If Rosetta thinks a rotamer is a low energy one, it’ll be taken forward to the next step. The one that’s output is the one that makes it through the process. There’s no quota based on the number of input conformers, so if you have one hundred conformers which are energetically infeasible and only one which can fit into the pocket, Rosetta will pick the one which fits in the pocket every time, despite it being vastly outnumbered.

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