AQUARIUS2: Knowledge‐based modeling of solvent sites around proteins

The program AQUARIUS2 calculates probable positions for water molecules within the first hydration shell of any protein for which atomic coordinates are known. Like its predecessor, AQUARIUS, it uses a knowledge of water molecules sites from crystallographically determined protein structures. Energy calculations are not employed. It differs substantially from the original program in that a 3‐D probability map (for solvent sites) is generated around the surface of the protein instead of the previously used discrete points. The accuracy of the program has been gauged by comparison with experimentally derived water molecule positions for proteins not used in the knowledge base of the program. It has also been tested by combining the probability density maps with crystallographically determined electron density maps for the protein porphobilinogen deaminase. This procedure filters the most likely solvent electron density peaks from the background noise and has been used in the determination of the solvent structure around the protein nerve growth factor.