Subject: CCL: Summary of program to determine structurally important water molecules

From: "Donald Keidel" <dopetec-.at.-dslextreme.com>
Date: Tue, 30 Mar 2004 14:00:15 -0800

I have summarized the responses I have received regarding finding a program
that can determine structurally important water molecules in crystal
structures.  Here are the responses I received.  Thank you to all that have
responded....all responses have been very helpful.  Have a good day.

Don

Dear Donald,
this is not a silly question. Some time ago a collegue of mine posted a 
question same to yours, and discussion continued for weeks.
The right answer doesn't exist.
At my experience, the best program to manage water positions (especially 
> from pdb by xray structures) is GRID. (http://www.moldiscovery.com) It is
really powerful and includes a special keyword LEAU to analyze 
about water position.
In the most straightforward way you could evaluate your structure using 
a water probe, and you can keep only water molecules that make strongest 
interactions.
Wonderful is that GRID it's free for academics. (if I well remember) Hope
this can help you, my best whishes, Stefano

Dear Don

 I fitted some functions that can distinguish between these two types of
water molecules, on the one hand structural or tightly-bound and on the
other losely bound or not that important (or reliable) from the pdb
structure of the protein. They are easy to use (or code up) and employ the B
factors of water molecules, their solvent accessible contact surface area,
and number of protein contacts within 3.5 Angstroms (optionally, also the
water molecule hydrogen bond energy as determined by WHAT IF). You can see
get the coefficients from the paper:

J. Mol. Model. 2003, Vol. 9, issue 3, pages 172-182

or through my webpage. Hope this helps and good luck

Alfonso

Hi Don, 

There's a program that I've used to locate water molecules that are in sites
of good iteraction energy.  The program is called "MMC" and is available
> from Dr. Mezei at Mt Sinai School of Medicine
http://inka.mssm.edu/docs/molmod/mmc.html The 'Structurally important'
aspect will have to come from somewhere else.. But at least you would be
able to say that there is a water here based on energetic considerations. It
allows you to both conduct a Grand Canonical Ensemble simulation where by
lowering the chemical potential, you can find conserved water,  

Resat H, Mezei M. Grand canonical ensemble Monte Carlo simulation of the
dCpG/proflavine crystal hydrate. Biophys J. 1996 Sep;71(3):1179-90. PMID:
8873992 

Or, you if you have the results of an explicit solvent simulation (either MC
or MD), you can analyse them to find 'Generic Sites'.  The program will
report these, and their %occupancy throughout the trajectory.  

Best Wishes, 

Josh

Hi Don,

I've got a simple program called pdbdist, which reads a PDB file, and finds
the closest
atoms/molecules from a given reference atom. It works under UNIX, and all
you have to do
is compile it. With the program, you may find waters within the active site
or so.

Whether or not there are (other) water molecules that are structurally
important,
is another question. However, you should realize that when there are crystal
waters present
in a PDB file, they are already well defined, e.g. structurally important;
said otherwise,
if a water molecule moves around all the time, it is not well defined enough
to be
characterized by X-ray crystallography, and probably is less important.

Donald,
GRID can do that, it is available for
UNIX,it is free.

Gabriele Cruciani

checkout out dowser by Jan Hermans (UNC chapel hill).

David.

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-----------------------------------
Donald J. Keidel
University of California, Riverside
Department of Biochemistry and Molecular Biology
Riverside, CA 92521
phone:  (909) 787-5493
fax:  (909) 787-4434
dopetec-.at.-dslextreme.com
webpage: www.biochemistry.ucr.edu/gru/gradstudents/don_keidel/index.htm