From owner-chemistry ":at:" ccl.net Tue Jan 17 13:50:00 2006
From: "Elaine Meng meng],[cgl.ucsf.edu" <owner-chemistry!=!server.ccl.net>
To: CCL
Subject: CCL: Questions on the protonations of a HIV-1 protease (1aaq)
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X-Original-From: Elaine Meng <meng|*|cgl.ucsf.edu>
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Date: Tue, 17 Jan 2006 10:01:46 -0800
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Sent to CCL by: Elaine Meng [meng,,cgl.ucsf.edu]
Hi Guosheng,
This paper may be useful. There is a short discussion of the active  
site Asp residues in HIV-1 protease (p. 714).

Li H, Robertson AD, Jensen JH.
Very fast empirical prediction and rationalization of protein pKa  
values.
Proteins. 2005 Dec 1;61(4):704-21.
PMID: 16231289

Also, in simulations, people have often protonated one of the active  
site Asp residues.  AMBER, for example, includes an ASH residue that  
could be used in this case.  I don't have a specific reference, but  
you could just search in PubMed for simulation studies on HIV1PR to  
see what others have done.

-----
Elaine C. Meng, Ph.D.                          meng::cgl.ucsf.edu
UCSF Computer Graphics Lab and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco
                      http://www.cgl.ucsf.edu/home/meng/index.html


On Jan 16, 2006, at 1:17 PM, Guosheng Wu wu_guosheng2002%%yahoo.com  
wrote:

> Sent to CCL by: Guosheng Wu [wu_guosheng2002[*]yahoo.com]
> Dear listers,
>
> I am puzzled in assigning protonation states for some HIV-1  
> protease complexes, and 1aaq(pdb code)
> is a typical complex of many structures.
>
>> From this structure, one can see all of the 5 oxygen atoms (from  
>> Asp 25 & Asp 125, and ligand OH)
> are very close to each other(2.7~3.1), and almost in the same  
> plane.  Also each of the Gly 27 is
> not far away(about 3.3 Angstrom) from the Asp 25, although the  
> angle of H-bond is not very good
> (the Xray resolution is 2.5 Angstrom, exp. done in 1992; only one  
> water is given, but not close to
> this part).
>
> Since the OO contact between Asp 25 and Asp 125 is 2.5 Angstrom,  
> which is about the distance of OO
> in H5O2+ ion(2.4), one would like to assign a proton between them.   
> However, it seems very
> difficulty to rationalize other polar interactions.
>
> One possible explanation may have something to do with quantum  
> effect, which may lead to some
> modifications over the hybridization of the ligand Oxygen atom, as  
> well as some of the C-O-H bond
> angles.  Certainly, some kind of minimizations may be able to help  
> on some directions, but it
> seems to me typical current force field would have trouble for this  
> case.
>
> I wonder if you have done any study on this special complex, or  
> similar cases (actually many pdb
> structures are like this one).  I would really appreciate if you  
> could share some of your insights
> with me.
>
> Best regards,
> Guosheng