Thanks everyone! This has been very helpful. I’ll go ahead and run the docking without symmetry. In order to avoid redundancy in the locations available for the docking, I’ve limited the layer of A to one hexamer and two monomers each from adjacent hexamers to include two-fold and three-fold interfaces between hexamers. However, this still contains a number of repetitive units. Here’s an example of why this is a problem for me: Suppose I have two docking runs. In Run1, A (the protein being docked) docks to M1, a subunit of the hexamer in the layer of B. In Run2, A docks to M2, a non-adjacent subunit in the same hexamer in a layer of B. In both runs, let’s suppose A is not in contact with any adjacent subunits, though in other runs, the docking interface could extend across anywhere from 1 to 6 subunits of B. These will have very different RMSD values, while if we superpositioned the two solutions by M1 and M2, we might find that A is in an almost identical position in each. Due to the fact that there are 10 identical subunits of B in this run (and all are necessary), this indicates that a large percentage of the results will be highly repetitive but not obviously so. I think an easy way to fix this would be to use constrains. I’ve read about site constraints in Rosetta++ and would like to penalize any docking solutions that do not place A in any contact with one specific subunit in the hexamer of B while allowing contact with all other subunits, but I don’t know of a way to do this in Rosetta 3.2.1. I’ve already read the constraint documentation, but I don’t see any mention of penalty site constraints, and it is not clear if I can penalize a solution that does not place any atom of A in contact with any atom of one specific chain of B. Any help would be appreciated.