Subject: Summary: Molecular Diversity - 2

From: "Elena Fioravanzo" <[email-masked]>
Date: Thu, 1 Jun 2000 14:54:35 +0200

Dear CCL members,

Please find my original question and replies (new and old ones).
Thanks a lot to collegues who contributed.

=================
there are many methods and indices to estimate molecular similarity, but it
is quite difficult to estimate-calculate molecular diversity.
Could someone give me, please, references (articles, web-site, softwares)
about this point?
=================

A >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
These are other articles you might find useful:

1) "Measuring Molecular Diversity: Evaluation of Alternative Subsets
Selected from Reagent Building Block Libraries for Combinatorial Chemistry."
Blankley, C. J., Pharm. Pharmacol. Commun. 1998, 4, pages 139-146

2) "The Diversity Challenge in Combinatorial Chemistry." Kauvar, L. M. and
Laborde, E., Drug Discovery and Development 1998, 1, pages 66-70

3) "Validated Descriptors for Diversity Measurements and Optimization."
Martin, Y. C., Bures, M. G. and Brown, R. D., Pharm. Pharmacol. Commun.
1998, 4, pages 147-152

4) "Assesing Similarity and Diversity of Combinatorial Libraries by Spatial
Autocorrelation Functions and Neural Networks." Sadowski, J., Wagener, M.
and Gasteiger, J., Angew. Chem. Int. Ed. Engl. 1995, 34, pages 2674-2677

5) "Novel Software Tools for Addressing Chemical Diversity" R. S. Pearlman,
Laboratory for Molecular Graphics and Theoretical Modeling, College of
Pharmacy, University of Texas (From June/July, 1996). You can read this
article on line at http://www.netsci.org/Science/Combichem/feature08.html

6) "Computational methods in molecular diversity and combinatorial
chemistry." Bures, M.G., and Martin, Y.C., Curr. Opin. Chem. Biol. 1998, 2,
pages 376-380

7) "Targeted molecular diversity in drug discovery: Integration of
structure-based design and combinatorial chemistry."  Li, J., Murray, C.W.,
Waszkowycz, B., and Young, S.C., Drug Discovery Today 1998, 3, pages 105-112

I hope this helps.

Guillermo Morales
-----
Guillermo A. Morales
Morales Consulting
E-mail: [email-masked]
Website: http://www.combichemlab.com
Member of the Combi-Web Consortium: http://www.combi-web.com

B >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Dear Elena,

We have written three very extensive reviews on the subject. Note that the
last one
is still in press. Hope that helps.
1.        D. K. Agrafiotis*, "Diversity of chemical libraries", in The
Encyclopedia of Computational Chemistry; Schleyer, P.v.R.; Allinger, N. L.;
Clark, T.; Gasteiger, J.; Kollman, P. A.; Schaefer III, H. F.; Schreiner, P.
R., Eds., John Wiley and Sons, Chichester, 1998, Vol. 1, 742-761.

2.        D. K. Agrafiotis*, J. P. Myslik, and F. R. Salemme, "Advances in
diversity profiling and combinatorial series design", in Annual Reports in
Combinatorial Chemistry and Molecular Diversity, Pavia, M., and Moos, W.,
Eds., Kluwer, 1999, 2, 71-92.

3.        D. K. Agrafiotis*, V. S. Lobanov, D. N. Rassokhin, and S.
Izrailev, "The measurement of molecular diversity", in Virtual Screening of
Bioactive Molecules, H.-J. Böhm, H.-J., and Schneider, G., Eds., Wiley-VCH,
Weinheim, in press.
---
Dimitris K. Agrafiotis, PhD              | E-mail: [email-masked]
3-Dimensional Pharmaceuticals, Inc.      | Tel:    (610) 458-6045
665 Stockton Drive, Suite 104            | Fax:    (610) 458-8249
Exton, PA 19341

C >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Hi Elena,

I wrote a little program which helps you to select a maximally diverse
subset of compounds from a large set of compounds, based on any number of
numerical descriptors you have available.  The program is based on
maximizing the mean nearest neighbor distance in multidimensional parameter
space.  You have to provide an input file with all the descriptors for all
the compounds in your set.  The program first normalizes all the data (so
that molecular weight doesn't overwhelm logP, for example).  Then it
selects random subsets, evaluates their similarity (using mean nearest
neighbor distance), and uses a genetic algorithm to select better and
better subsets.

* D. Eric Walters, Ph.D., Associate Professor, Biochemistry & Molecular
Biology
* Finch University of Health Sciences/The Chicago Medical School
* 3333 Green Bay Road, North Chicago, IL  60064
* ph 847-578-8613;fax 847-578-3240; email: [email-masked]
* "A man would do nothing if he waited until he could do it so well that
*  no one would find fault with what he had done." --Cardinal Newman
* * * visit my web page! http://www.finchcms.edu/biochem/walters.html * * *

D>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Dear Elena,

Here are two of our papers, which include a number of useful references:

1- Molecular diversity and its analysis.
D. Gorse, A. Rees, M. Kaczorek and R. Lahana
Drug Discovery Today, Vol.4 No. 6,  June 1999.

2- Functional diversity of compound libraries.
D. Gorse and R. Lahana
Current Opinion in Chemical Biology, Vol.4 No.3, June 2000.

Hope it helps,

Roger

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Tel: +33 (0)466 048 668 (Direct)         Fax: +33 (0)466 048 667
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E >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
While by no means complete, here is a list that could get you started.

1.      Van Drie, J. H., Lajiness, M. S. 1998. Approaches to virtual library
design. DDT 3:274-83
2.      Pearlman, R. S., Smith, K. M. 1998. Software for chemical diversity
in the context of accelerated drug discovery. Drugs of the Future 23:885-95
3.      Hassan, M., Bielawski, J. P., Hempel, J. C., Waldman, M. 1996.
Optimization and visualization of molecular diversity of combinatorial
libraries. Molecular Diversity 2:64-74
4.      Jamois, E. A., Hassan, M., Waldman, M. 1999. Evaluation of
Reagent-Based and Product-Based Strategies in the Design of Combinatorial
Library Subsets. J. Chem. Inf. Comput. Sci. 40:63-70
--
Jeffrey L. Nauss, PhD           Phone: (858) 799-5555
Customer Training Programs      Fax: (858) 458-0136
Molecular Simulations Inc.      E-mail: [email-masked]
9685 Scranton Road              http://www.msi.com/about/events/training
San Diego, CA 92121-3752

F >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Go to http://cisrg.shef.ac.uk and look under Recent Work for the program
SELECT and accompanying references.
Nick ([email-masked])

G >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Molecular Diversity:
http://www.phar.cam.ac.uk/DDG/
Try our site and my supervisor's new book "Molecular Diversity in Drug
Design (1999)" Contact him  [email-masked] if and he might be
able to help. Quantitaive approaches depend on small molecule or binding
site diversity. Texts on QSAR might help.

James Smith
_________________________________________________________________________

 James Smith       Drug Design Group             01223 338 600 (College)
 St John's College Department of Pharmacology    01223 331 985 (Office)
 Cambridge         University of Cambridge       01223 331 740 (Fax)
 CB2 1TP           CB2 1QJ                       07625 395 084 (Pager)
 United Kingdom    United Kingdom              [email-masked]
  http://www.cus.cam.ac.uk/~js252
_________________________________________________________________________

H >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
I suggest you to contact Dr. Antonio Jerez, at UNED Madrid:
 [email-masked]

*****************
Julio César Llópiz Yurell
IMRE, UH
Zapata y G, Habana 10400, CUBA
Tel (537) 781182  Fax (537) 334247

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