Subject: Re: CCL:Seeking information in two areas...

From: "Osman F. Guner" <[email-masked]>
Date: Mon, 07 Aug 2000 23:55:37 -0500

HipHop pharmacophores are prioritized based on how well the training set 
fits onto a pharmacophore.  The following two papers may provide more 
information.

         Greene, J.; Kahn, S.; Savoj, H.; Sprague, P.; Teig, S. "Chemical 
Function Queries for 3D Database Search", J. Chem. Inf. Comput. Sci., 1994, 
34, 1297-1308.

         Clement, O. O.; Trope-Mehl, A. "HipHop: Pharmacophores based on 
multiple common-feature alignments," in Pharmacophore Perception, 
Development, and Use in Drug Design, Güner, O. F. Ed., Int. Univ. Line, 
2000, La Jolla, 69-83.

I have been proposing follow up database searching and evaluation of the 
search results to validate pharmacophores.  Analysis of several metrics are 
published, together with the GH-score which is a weighted linear 
combination of two factors that address the selectivity as well as coverage 
of pharmacophores at:

Güner, O. F.; Henry, D. R.  "Metric for analyzing hit lists and 
pharmacophores," in Pharmacophore Perception, Development, and Use in Drug 
Design, Güner, O. F. Ed., Int. Univ. Line, 2000, La Jolla, 191-211.

Most of the above are covered in some details in "the Pharmacophore 
book".  Go to www.amazon.com or www.barnesandnoble.com and search for the 
keyword "pharmacophore."  A detailed review of the book (written by Lisa 
Balbes) can be found at ChemWeb 
http://www.chemweb.com/alchem/2000/books/bk_000728_osman.html

As far as conformational diversity, see the following three papers and 
references within:

Smellie, A.; Teig, S. L.; Towbin, P. "Poling: Promoting Conformational 
Coverage", J. Comp. Chem., 1995, 16, 171-187.

Smellie, A.; Kahn, S. D.; Teig, S.  "An Analysis of Conformational Coverage 
1. Validation and Estimation of Coverage", J. Chem. Inf. Comput. Sci., 
1995, 35, 285-294.

Smellie, A.; Kahn, S. D.; Teig, S.  "An Analysis of Conformational Coverage 
2. Applications of Conformational Models", J. Chem. Inf. Comput. Sci., 
1995, 35, 295-304.

Hope this helps a bit.  Thx...osman

At 07:06 PM 8/3/00 -0400, Joe M Leonard wrote:
>Folks,
>
>When I was at ACS SF in 1997, several of us discussed whether
>there were any published methods to score pharmacophores without
>having to do the search(es) and compare the results.  The lunch-
>consensus was that nobody had done this, and that it was an
>interesting area...  Therefore, were we wrong in 1997, or has
>there been work done since then that I should be aware of?
>
>
>Also, I am interested in investigating conformational diversity,
>and seek similar information.  I've got some ideas, but hate to
>reinvent wheels...  Are there particular papers I should run
>down, or people I should talk to?
>
>Pointers, citations, whatever appreciated!  If the responses
>are good, I'll summarize...
>
>Joe
>
>P.S. If people want to talk about this, I'll be at EuroQSAR
>(and at ACS for a short while).
>
>
>-= This is automatically added to each message by mailing script =-
>[email-masked] -- To Everybody    |   [email-masked] -- To 
>Admins
>[email-masked] -- HELP CHEMISTRY or HELP SEARCH
>[email-masked] -- archive search    |    Gopher: gopher.ccl.net 70
>Ftp: ftp.ccl.net  |  WWW: http://www.ccl.net/chemistry/   | Jan: [email-masked]
>
>
>
>

---
Osman F. Güner, Ph.D.
Director,  Lead Identification & Optimization
Molecular Simulations Inc.   (858) 799-5341
[email-masked]        http://www.msi.com