4. Last, we reconstructed the original interaction sites of the cholesterol model as closely as possible using virtual sites. During such a reconstruction one has to balance the computational complexity of a virtual site of a given type and the difference between the original and reconstructed positions of the interaction sites. Naturally, one should thoroughly test the ability of the optimized model to reproduce the relevant properties of the original model. All these considerations can in principle be explicitly taken into account as constraints applied to the optimization scheme.