Subject: Re: CCL:Simulations in Combinatorial Chemistry

From: Ronald D Ferguson <[email-masked]>
Date: Tue, 23 Jan 1996 19:14:34 -0700 (MST)

On Thu, 18 Jan 1996, Thomas Wieland wrote:

> ...I try to learn more about Combinatorial Chemistry.... 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.
> 
> Has anyone experiences in that field? I would be grateful to receive some
> pointers to literature describing the rules and techniques of building
> combinatorial libraries in simulation (or anything in this direction).
> 
> I would also be happy to find some experts willing to answer my questions
> once in a while (isn't this the aim and the advantage of the e-mail age?).

Dear Thomas Wieland,

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

Good Luck,

Ron Ferguson
Selectide, the Tucson CombiChem site of HMR

[email-masked]