UNC Computational Structural Biophysics Group

DOWSER program


LAST UPDATED: April 2003. The version of February 2003 is useless without this correction.
PREVIOUSLY UPDATED: February 2003. This update corrects problems with the dowserx script (which places water in crevices).


by: Jan Hermans, Xinfu Xia, Li Zhang, Dave Cavanaugh
Department of Biochemistry and Biophysics
School of Medicine
University of North Carolina
Chapel Hill, NC 27599-7260

Dow'se (dous) v.t., v.i., to search for subterranean supplies of water by the aid of a dowsing rod. [orig. unknown] - dow'ser, n. Fr. sourcier. Du. wichelroedeloper. G. Wünschelrutelaufer. It. rabdomante.


Purpose:

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).


Usage:

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.


Dowser-3 much improved:

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

·  polar hydrogens are automatically added to the structure

·  the optimization of position and orientation of the water molecules in the internal sites is at least 10 times faster than before

·  a set of four output files in pdb format is produced for easy comparison via molecular graphics:

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.


Working with nucleic acid molecules in Dowser (2005):

In 2005, Cameron Mura (now at the University of Virginia) 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 a web page maintained at UVa, a copy of which is made available via this web site (at UNC).


Related website:

The SOLVATE program 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.


Obtain program code and instructions:

For security, there is no ftp demon running on this machine. 

To download a copy of the Dowser program, click on dowser and ‘save’.


Examples:

(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

I. Hofacker and K. Schulten. Oxygen and proton pathways in cytochrome c oxidase. Proteins: Struct. Funct. Genet., 30:100-106, 1998.