is it possible to restrict a space in Rosetta Design… like use some dummies guaranteeing that positions in this area are not to large thus blocking space… or do I have to restrict the surrounding amino acids going for small ones and just hope that´s enough.
The most straightforward way to tell Rosetta not to fill space is to put something in the space. If you think a ligand goes there, and you know what the ligand is, then make a parameters file for it and use either the ligand docking/design tools or fixbb. If you just want to leave an empty pocket; no, there isn’t a straightforward way to do it. I can think of a few things to try that involve writing new code; with out-of-the-box Rosetta your best bet is to use small residue types as you suggest.
Keep in mind there’s some facility for repulsive-only atom types in Rosetta, so if you know “something” goes there, but don’t want anything in particular, you can make a repulsive only ligand to keep other atoms out.