As rosetta want to predict the 3D shape of proteins in real biological systems. Does it take interaction with surrounding molecules into account. In biological systems that should be mostly water. Since water can undergo strong interactions with aminoacids, there is the possibilty (at least in my understanding) that the overall minimum in energy may be different if interactions between water and the outer sphere of the protein are considered or not.
In short, is the surrounding for the folding process considered as homogenous or heterogenous?

As rosetta want to predict the 3D shape of proteins in real biological systems. Does it take interaction with surrounding molecules into account. In biological systems that should be mostly water. Since water can undergo strong interactions with aminoacids, there is the possibilty (at least in my understanding) that the overall minimum in energy may be different if interactions between water and the outer sphere of the protein are considered or not.
In short, is the surrounding for the folding process considered as homogenous or heterogenous?

Excellent question! Yes, rosetta takes account of the fact that the surrounding environment is almost entirely water, and as you suggest this is critical for computing energies accurately.

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