Subject: Summary - molecular symmetry

From: "W. Huber" <[email-masked]>
Date: Thu, 15 Apr 1999 05:29:29 +0200 (MET DST)

Thanks to Mark Zottola, David Turner and Christian Lemmen for their 
replies. I had asked for information on 3d flexible molecular 
similarity methods, and in the following are the replies I got.

Best regards
W. Huber

------------------------------------------------------------
Dear Dr. Huber,

I believe two pieces of software may be of interest to you. The first
is Catalyst by Molecular Simulations. This does require you to define
regions of interest (pharmacophores such as hydrogen bond
donors/acceptors, regions of "grease" aliphatic aromatic regions,
etc.) on the "drug-like" molecule. But it does an extremely good job
of defining conformational space occupied pharmacophores and searching
as well. I am sure MSI can give you a better blurb about Catalyst's
capabilities, but from my experience, it does do a very good job in 3D
searching of databases.

The second piece of software I would recommend would be the MedChem
software by Daylight Che Information Systems. This does not have the
3D searching characteristics, but it can search 2D (flat databases)
for molecules which are similar for any given molecule or collection
of pharmacophores. The tool kit which comes with this software was
excellent for creating the search tools (fragments connected according
to certain rules), etc. I used both of these extensively while
interning at Glaxo. Both these programs proved to be extremely useful
in combinatorial design/analysis.

In fact, one can envision using Catalyst to screen the DB search
results from MedChem to energetically evaluate the cost of achieving a
conformation (or set thereof) which maximizes the similarity to the 3D
pharmacophore you are searching on.

I hope this helps.

Regards,

Mark A. Zottola                       Alabama Research and Education 
Network
119 Rust Research Center              Nichols Research Corporation
University of Alabama-Birmingham      VOICE:  (205) 934-3893
Birmingham, AL  35294                 EMAIL:  [email-masked]

------------------------------------------------------------

Hi

There is the field-based similarity searcher (FBSS) developed in
our Group. It compares molecules on the basis of steric, electrostatic
hydrophobic fields and uses a GA to optimise molecule overlays with 
similarity as the fitness function. Gaussian approximations to the
various distance-dependencies are used to speed-up the process.
Conformational flexibility is permitted of either or both the target and 
database compounds being searched.

See: 
Thorner, D.A., Wild, D.J., Willett, P. & Wright, P.M. (1996)? Similarity 
searching in files of three-dimensional chemical structures: flexible 
field-based  searching of molecular electrostatic potentials? Journal of 
Chemical Information and Computer Sciences, 36, 900-908
Wild, D.J. & Willett, P. (1996)? Similarity searching in files of 
3-dimensional chemical structures - alignment of molecular  electrostatic 
potential fields with a genetic algorithm? Journal of Chemical 
Information 
and Computer Sciences, 36, 159-167?

Regards
David Turner

Dr David Turner Dept of Information Studies, Sheffield University 
Sheffield, S10 2TN          Tel. 0114 2 222 650 E-mail: 
[email-masked]

------------------------------------------------------------

Lieber Herr Huber!

Ich sah ihre Anfrage bez"uglich alignment-tools
in der CCL. Da ich als Entwickler von FlexS
sicher nicht Vorurteilsfrei sprech m"ochte
ich Sie lediglich auf die Zentrale Publikation
zu FlexS hinweisen, die sicherlich einen
Gro\3teil ihrer Fragen abdeckt.

@ARTICLE{LemmenLK98,
author =        {C. Lemmen and T. Lengauer and G. Klebe},
title =         {{\sc FlexS}: A Method for Fast Flexible Ligand 
Superposition},
journal =       Journal of Medicinal Chemistry,
volume =        {41},
Xnumber =       {23},
year =          {1998},
pages =         {4502--4520},
}

Herzlichst,
-Christian Lemmen