The Dowser program surveys a protein molecule's structure to locate internal cavities and assess the hydrophilicity of these cavities in terms of the energy of interaction of a water molecule with the surrounding atoms. Experience has shown that cavities with interaction energies below -12 kcal/mol tend to be filled, and cavities for which the energy is greater than that threshold, tend to be empty (Zhang & Hermans, 1996).

The program requires as input the atomic coordinates in PDB format. First, the molecular surface of internal cavities is calculated with Connolly's MS program. (Actually, a faster, stripped-down equivalent.) Then Dowser produces as output a list giving the coordinates and the minimum energy value for placing water molecules starting from each point on the internal surface. The positions are sorted, when two positions overlap, the one with lowest energy is retained, and only water molecules with binding energy below -10 cal/mol are retained. The results can be viewed with programs such as rasmol or vmd.

A more detailed description is given in the Dowser manual.

The Dowser code underwent a major overhaul in February 1998. The new Dowser program has the following new or improved features:

1. coordinates of the protein atoms including polar hydrogens
2. coordinates of the internal surface points
3. coordinates of the internal water molecules present in the original pdb file
4. coordinates of the optimized low-energy water molecules placed by Dowser.

In 2005, Cameron Mura in the McCammon lab at UCSD developed additions to the dowser database that allow analysis of structures of nucleic acids and of protein-nucleic acid complexes. This is described in detail in an original web page maintained at UCSD, a mirror of which is made available via this web site (at UNC).

Related website:

The SOLVATE progam constructed by Helmut Grubmüller and Volker Groll can be used to construct an atomic solvent environment model for a given atomic macromolecule model (solute) for use in molecular dynamics simulations. It is advised to use this program for external solvation, and use Dowser for placement of internal water molecules.

To download a copy of the Dowser program via ftp, click on dowser.tar.gz.

For security, the ftp demon on this machine denies access from machines outside the ".edu" domain. If you wish to download DOWSER from outside this domain, please send mail to Jan Hermans, and the permission will be briefly reset. (If no reply within a few days, please contact Lisa Phillippie.) Please see note about denial of ftp access at the top of this page.

(1) Bovine pancreatic trypsin inhibitor (1BPI)

Figure B1 shows the crystal structure, extended with polar hydrogens, with three internal crystallographic water molecules. (This example is provided with the released Dowser code.)

Figure B2 shows the location of the internal surface

Figure B3 shows the four internal water molecules placed by Dowser

(The crystal structure contains coordinates of 167 water molecules, with a variety of B-factors and occupancies. One "strong" crystallographic water site is close to the most external of the four water molecules placed by Dowser, but apparently this crystallographic position was treated as external. From "The structure of bovine pancreatic trypsin inhibitor at 125 K", by Parkin, Rupp & Hope, published only as a pdb file).

(2) Actin

Figure 1 Shows a dry protein (actin, Kabsch, Mannherz, Suck, Pai & Holmes, Nature 347, 27-44, 1990).

Figure 2 shows water molecules selected by Dowser.

Figure 3 shows the combined view.

(3) Cyclophilin

Figure 4 shows the cyclophilin structure along with the buried water molecules determined by crystallographic refinement.

Figure 5 shows the water molecules determined by Dowser overlapped on the original picture.

(4) Cytochrome-c oxidase