Subject: Summary: Simulations in Combinatorial Chemistry

From: [email-masked] (Thomas Wieland)
Date: Thu, 25 Jan 96 14:14:37 +0100

Dear Netters,

last week I posted the following question to this list:

>I try to learn more about Combinatorial Chemistry. I have checked
>the NetSci issue last summer and some review articles like the ones
>by Gallop, Gordon, Barrat et al. (J. Med. Chem. 37). Most papers
>only tell how a combinatorial library is built experimentally. Since I have no 
>laboratory, but just a computer, I want to do this as a simulation,
>i.e. generate the diversity in a file and apply a similarity
>search (or any other) method for screening.
>Last spring there was a paper by T. Carell, J. Rebek et al. in
>Chemistry & Biology, which was quite detailed. Unfortunately
>I couldn't find any other.

I got 6 inquiries and 5 answers to it, but in general I have the feeling that 
there are more people out there who want to know than those who do know.
If in the future anybody else comes across with some interesting material, 
I will certainly be glad to hear about it, too.

Since some asked, the source of the paper cited above is:

"New promise in combinatorial chemistry: synthesis, characterization,
and screening of small-molecule libraries in solution"
T. Carell, E.A. Wintner, A.J. Sutherland, J. Rebek jr., Y.M. Dunayevskiy, 
P.Vouros
Chemistry & Biology, 1995, Vol. 2, No 3, p. 171-183

The other answers are as follows:

----------------------------------------------------------------------
From: [email-masked] (Dieter Poppinger)

There is a good paper by E.Martin in J.Medicinal Chemistry 38 (1995) p. 1431. 
Also there is something by Keith Davies in NetSci last year. Most other
stuff is just talked about at conferences. 

----------------------------------------------------------------------
From: Arthur Wang <[email-masked]>

I am a Ph.D student majoring in computer-aided drug design. I have 
developed a computer program to generate ligands which can fit to the 
target receptor. The method to construct molecular models is so-called 
"atom-growing". That is, I let different types of atoms to be grown from 
a seed fragment. And the most of important, I take account all possible 
combinations of atom patterns. So I can finally get a library for a 
specific receptor. Then a following program is used to evaluate the 
quality of binding of each molecule. To some extent, it is the simulation 
of combinatorial chemistry on computer.

You can look at my homepage. There is a brief abstract of my paper. The 
paper have been submitted to J.Chem.Inf.Comp.Sci for consideration. For 
more details, just contact with me.

-----------------------------------------------------------------------
From: "Alberto Gobbi" <[email-masked]>

J. Chem. Inf. Comput. Sci 1995, 35, 1026 may be interesting for you. It 
decribes some aspects which are realized in the Comb. Chem. software of 
Daylight Inc. (www.daylight.com). Which may be of big help for representing 
libraries.

-----------------------------------------------------------------------
From: "Malcolm A. Cline" <[email-masked]>

If you will send me a FAX number, I will FAX you an application
note using our software to build a combinatorial library.  The
library is a lead explosion around a single ACE (Angiotensin
Converting Enzyme) inhibitor.

(Remark: Unfortunately, I haven't got this yet.)
-----------------------------------------------------------------------
From: Ronald D Ferguson <[email-masked]>

Additional work on the subject which you address was expressed in an 
article by Dr. Martin from Chiron. In this J. Med. Chem. , 1995, Vol.38, 
9, 1431-1436 article, Dr. Martin explained a algorithm they devised to 
define the "molecular diversity" of a combinatorial chemical library.

As far as computational searches for structural diversity, "Chem-X" from 
Chemical Design as well as others have commercially available packages 
which will allow for such a "combinatorial chemical" search. These 
packages have publications of the theory and experiments which lead to 
the "final" programs. I can point you toward some of these references 
later if you wish, but I suggest that you look at the past four years of 
the Journal of Computer-Aided Molecular Design and the Journal of 
Molecular Graphics. Do a search (CAS or other) and pay attention to 
descriptors of "molecular shape", "3 dimensional data bases" and 
"structure retrieval systems". Names associated with these articles 
include the following:

Chris Ho
Garland Marshall
Guy Bemis
Irwin Kuntz
Andrew Poirrette
Peter Willett
Zlatko Mihalic
David ClarkShaun Jordan
Andrew Leach
R. Nilakantan
N. Bauman
R. Venkataraghavan
Gustavo Arteca
--------------------------------------------------------------------

Thanks to all you wrote to me.

Best regards,

Thomas Wieland               +---------------+
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