Extracting hydration sites around proteins from explicit water simulations

Two new methods are assessed for determining the location of hydration sites around proteins from computer simulation. Current methods extract hydration sites from peaks in the water density constructed in the protein frame. However. the dynamic nature of the water molecules, the nearby protein residues, and the protein reference frame as a whole tend to smear out the water density, making it more difficult to resolve sites. Two techniques are introduced to better resolve the water density. The first is to construct the water density from the time-averaged position of each water molecule in the protein frame while the water remains within a given distance of this averaged position. The second technique is to construct the water density from the time-averaged position of each water in the reference frame only of the nearby residues. Criteria for determining hydration sites from the water density are examined. Both techniques are found to significantly improve the detail in the water density and the number of hydration sites detected. (C) 2002 Wiley Periodicals, Inc.