UNC Computational Structural Biophysics Group
DOWSER program
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.
