How is the surface problem addressed?

1) One can artificially position waters, either in a simple way such as introducing a lattice of water around the protein, or in a more complicated fashion, such as using a molecular dynamics simulation.

2) One can survey crystal structures of molecules solved to relatively high resolution which contain fixed water positions at high occupancy.

The observed trend for Voronoi volumes of surface atoms is that they tend to be ~7% larger than buried atoms.

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