Subject: summary about find water in a hydrophobic site

From: maoxiang <[email-masked]>
Date: Sat, 03 Jul 1999 20:40:52 +0900

Hi, everyone:
 
     I have sent a question about find the water molecule in an high
hydrophobic place. My question is the following:

--------------------------------------------------
I have docked the substrate in the active site, but in the reference, it
reports that there are water molecules involved in the reaction. But the
problem is the active site and the substract is highly hydrophobic, it
have some aromatic rings. When I do molecular dynamics with insightII, I
put 3-4 layers of water around the complex, fix the parts far away from
the active site. but the water all escaped at the end.I know I can
tether the water molecules, but I do not know the exact position.Does
anyone has the experiences to find the proper water positions. 
---------------------------------------------------------
    
    I received two answers, here I want to thank them. They are Mr.
Carlos Faerman and Mr. David Maxwell. 
   
    Carlos recommend a reference to me, it is "Consensus preferred
hydration sites in six FKBP12-drug complexes. Proteins:Structure,
Function and Genetics 23, 1 (1995). Carlos H. Faerman and Andrew Karplus
". 
    
    Mr. David Maxwell gave the following answer:
---------------------------------
You can use a restraint in InsightII that only takes effect if the water
attempts to go beyond a certain amount and essentially zero elsewhere. 
This
effectively allows for the creation of a sphere around the binding site
that
penalizes any water trying to escape.  Look in the manuals regarding
restraints
and you will find what I'm talking about.  I've used this to do
simulations of
single organics and binding sites of proteins and it seems to work
okay.  It
sure beats watching the waters fly away!
------------------------------------------
    
   All of the above methods need a great amount calculation in the work.
And here I find a way to find the water in the active site, I used
AUTODOCK to find it. First I have docked the ligand in the active site,
and then merge it to the protein to form a whole one, and them dock the
waters to the active site. I do not known if I am right to use AUTODOCK
here, but I found it. And now I have more work to do about the QM/MM. 
   Thank you again for your answers.

With my best wishes,
Mao
  ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
|  Mao Xiang                                                      |
|  Lab of Molecular Regulation for Microbial Secondary Metabolism |
|  Shanghai institute of Plant Physiology, Academia Sinica        |
|  300 Fenglin Road, Shanghai, China, 200032                      |
|  Tel: +86-21-64042090-4791                                      |
|  Fax: +86-21-64042385                                           |
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