I’m not clear on what -interface mode was. It was a mode in Rosetta 2.x; I used it briefly in fall 2006 and haven’t touched it since. I think it was for calculating ddGs of binding for interface mutations at protein-protein interfaces; so by “different ligands” they mean essentially the same structure with small sequence changes, not different binding partners. There is a paper or two on ddGs in Rosetta3 being prepared by the community.
It’s perfectly reasonable to make a graph of predicted versus experimental ddGs, but your correlation will top out at .6-.7, depending on a variety of factors. (We are of course working towards unity!)
All rosetta outputs are approximations because our energy function isn’t reality’s energy function.