Subject: Re: molecular similation

From: Irene Nobeli <[email-masked]>
Date: Fri, 1 Oct 1999 10:10:07 +0100 (BST)

Dear all

Some time ago I asked two questions. One was whether anyone knows of a
database of all small molecules that can be found in cells, or the
metabolome as I believe it is called. Unfortunately I received no
answer to this question.

My second question concerned software for determining molecular
similarity (preferably available in the public domain). I am grateful to
all the people who helped with their answers, which I copy below.

Thank you all again,

Irilenia

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>From [email-masked]  Mon Sep 13 16:37:01 1999
......
Anyway, I have this program for doing similarity measurements/alignments,
that was based on the original SEAL (Steric and Electrostatic ALignment)
code of Kearsley and Smith.  My program (called 'walrus') uses a much
more sophisticated model for assessing the similarity, but this may be
regarded as overkill for most cases (each calculation on a small molecule
takes a few hours on an Octane; SEAL takes a few seconds) and is probably
best restricted to calibration.  It is also a pig to use.  And it takes
its input from Gaussian.  But please let me know if you are interested.

The SEAL code itself (fortran, but you need to make a couple of changes to
get it to compile on an SGI) was supplied on a floppy disk with the
original publication.  I had all sorts of trouble getting this (floppy
disks degrade quite quickly...), so, again, please let me know if you are
interested.

Good references to get you started are:

@article{kears:seal,
  author  = "S. K. Kearsley and G. M. Smith",
  title   = "An alternative method for the alignment of molecular
             structures: maximising electrostatic and steric overlap",
  journal = "Tetrahedron Computer Methodology",
  volume  = 3,
  pages   = "615--633",
  year    = 1990,
  note    = "Includes original Fortran-77 source code for SEAL program."}

@article{meyer:molecsim,
  author  = "A. Y. Meyer and W. G. Richards",
  title   = "Similarity of molecular shape",
  journal = "Journal of Computer-Aided Molecular Design",
  volume  = 5,
  pages   = "427--439",
  year    = 1991}

@article{richards:hrindex,
  author  = "E. E. Hodgkin and W. G. Richards",
  title   = "A semi-empirical method for calculating molecular similarity",
  journal = "Journal of the Chemical Society, Chemical Communications",
  pages   = "1342--1344",
  year    = 1986}

@incollection{dean:drugs,
  author  = "P. M. Dean",
  title   = "Defining molecular similarity and complementarity for drug design",
  booktitle="Molecular Similarity in Drug Design",
  pages   = "1--21",
  editor  = "P. M. Dean",
  publisher="Chapman and Hall",
  address = "London",
  year    = 1995}

@incollection{good:drugs,
  author  = "A. C. Good",
  title   = "3D molecular similarity indices and their application in
             {QSAR} studies",
  booktitle="Molecular Similarity in Drug Design",
  pages   = "1--21",
  editor  = "P. M. Dean",
  publisher="Chapman and Hall",
  address = "London",
  year    = 1995}

Being nearby, you might also like to look in my thesis, which should be in
the University of London library (C. S. Page, PhD, 1998).  The final
chapter ("Measuring Chirality") has a (fairly) comprehensive review.

Hope this helps.

best wishes,

Chris Page
Uni. Valencia

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>From [email-masked]  Mon Sep 13 17:21:07 1999

...............
You could use the programs in New Arthur package, they are for clustering
compounds using PCA, KNN and SIMCA methods, he is free.
In order to calculate the phusico-chemical properties you could use WHIM
3D program he is also free and could be found in the inthernet to
download, but has one problem, some parameters do'n't have
physico-chemical significance, they are only mathematical. And you
couldn't use them to derive QSAR models.
You could also, finde COMFA for pc's free in the inthernet.
I don't know any program that could calculate PLS and neural networks, two
other clustering programs, inthe net for free, the are in TSAR package
>from Oxford Molecular.
For generate equations, QSAR equations, I thing you could use the Bilin
program, I think he is free too.
I hope that could help you. 
If you're interested, my group here in Brazil has some good experience 
with clustering methods. If I could help more, let me know.
Best Regards

 ___________________________________________________________________
|                                                                   |
|Antonio Luiz Oliveira de Noronha   -   [email-masked] |
|Medicinal Chemistry of Organotin Compounds                         |
|NEQUIM - Medicinal Chemistry Group                                 |
|Chemistry Departament - DQ                                         |
|UFMG - Federal University of Minas Gerais - Brazil                 |
|Av. Antonio Carlos, 6627 - Campus Pampulha                         | 
|CEP 31270-901 - Belo Horizonte - MG - Brazil                       |
|VOICE +55 31 499 5765   -   FAX +55 31 499 5700                    |
|___________________________________________________________________|

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>From [email-masked]  Mon Sep 13 22:09:16 1999

.............
You might want to look at two articles by Rob Brown and me:

1)Brown, R. D.; Martin, Y. C. Journal of Chemical Information and Compu=
ter
Sciences 1997, 37, 1-9.
2)Brown, R. D.; Martin, Y. C. Journal of Chemical Information and Compu=
ter
Sciences 1996, 36, 572-584.

Also of course, there are many articles by Peter Willett on diversity.
1)Turner, D. B.; Tyrrell, S. M.; Willett, P. Journal Of Chemical Inform=
ation
And
Computer Sciences 1997, 37, 18-22.
and a whole issue of PD3 devoted to the topic.

Attached are a couple of my articles.

1)Martin, Y. C. Perspectives in Drug Discovery and Design 1997, 7/8, 15=
9-172.
2)Martin, Y. C.; Brown, R. D.; Bures, M. G. "Quantifying Diversity"; Ke=
rwin,
J. F.
and Gordon, E. M., Ed.; Wiley: New York, 1998, pp 369-385.

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
>From [email-masked]  Tue Sep 14 12:43:03 1999

.................
I was wondering, there is another kind of physico-chemical parameters that
you could use in QSAR.
They are called quantum descriptors, and you could use GAMESS, that are
free ab initio program to calculate them
Best Regards 

>From [email-masked]  Thu Sep 30 01:50:06 1999
..............

>From what I heard at an AAPS meeting in Washington recently, the BCUT
molecular diversity measures are good at clustering molecules with similar
targets.  These derive from some work on molecular eigenvalue indices first
published by Frank Burden in J. Chem. Inf. Comput. Sci. in the late 80s
aand turned into the Diverse Solutions software by Bob Pearlman at Uni
Texas.  I believe Tripos Associates (http://www.tripos.com) sell the
software or Pearlman may release it to academic researchers.

Cheers,

Dave

Dr. David A. Winkler                    Email: [email-masked]
Senior Principal Research Scientist     Voice: 61-3-9545-2477
CSIRO Molecular Science			Fax:   61-3-9545-2446
Private Bag 10,Clayton South MDC 3169   http://www.csiro.au
Australia 	        		http://www.molsci.csiro.au

>From [email-masked]  Thu Sep 30 20:51:36 1999
............

Dra. Irene Nobeli
The WHIM 3D program you could dounload at this site:
www.disat.unimi.it/chm

The New Arthur package is a package for clustering analysis emploing SIMCA
analysis, KNN and PCA, this cluster programs are all included.
Do you have some experience with this kind of cluster algoritm?
You could contact Dr. Bruns at this mail : [email-masked]
Bilin is a program to perform bilinear analysis, correlating your
biological activity with the phisico-chemical parameters.

CoMFA - SoMFA you should search in the ccl homepage. There you will find
where you could get this program. He perform a comparative field analysis
QSAR 3D with your data and the biological activity.

I hope this could help. Please fell free to ask questions that you have!

Best Regards
 ___________________________________________________________________
|                                                                   |
|Antonio Luiz Oliveira de Noronha   -   [email-masked] |
|Medicinal Chemistry of Organotin Compounds                         |
|NEQUIM - Medicinal Chemistry Group                                 |
|Chemistry Departament - DQ                                         |
|UFMG - Federal University of Minas Gerais - Brazil                 |
|Av. Antonio Carlos, 6627 - Campus Pampulha                         | 
|CEP 31270-901 - Belo Horizonte - MG - Brazil                       |
|VOICE +55 31 499 5765   -   FAX +55 31 499 5700                    |
|___________________________________________________________________|

------------------------------------------------
Irene (Irilenia) Nobeli
Biomolecular Structure and Modelling Unit
Department of Biochemistry and Molecular Biology
University College London
Darwin Building
Gower Street
London
WC1E 6BT

[email-masked]
0171-419 3890
0171 504 2171

>>> The gene pool could use a little chlorine. <<<