Subject: Homology: Studies

From: Mr Andrew D Allen <[email-masked]>
Date: Wed, 23 Feb 94 15:41:02 GMT

As promised here is the summary of replies on Homology studies.

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>From [email-masked] Tue Feb 22 14:14 GMT 1994

HOMOLOGY by Biosym (San Diego, CA) has an integrated package to search
sequence databases and make homology 3D model. I have used it for
several years with satisfaction.

_____________________________________________________________________
Joseph G. Major, Ph.D.  [email-masked]
(713)664-2288 (voice)	(713)664-8914 (fax)

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>From [email-masked] Fri Feb 18 19:06 GMT 1994

Dear Mr. Allen:

   There is plenty of code to do standard 1D/1D peptide sequence matching
which dates back to the Needleman-Wunsch algorithm.[1]  One package which
contains several variations of this matching algorithm is the GCG software.[2] 

[1] Needleman, S. B.; Wunsch, C. A general method applicable to the search for
    similarities in the amino acid sequence of two proteins.  J. Mol. Biol.  
    1970, 48, 444-453. 

[2] Genetics Computer Group, (1991), Program Manual for the GCG
    Package, Version 7, April 1991, 575 Science Drive, Madison, Wisconsin, 
    USA  53711.

    More recently, there has been a great deal of interest in methods for
finding which 3D protein structure is compatible with a given 1D sequence (the
inverse protein folding problem).  This software is potentially useful for
finding structures which despite their low primary sequence homology,
nevertheless share similar protein folds. Below is a summary of the responses
to my query to the bionet.biology.computational mail newsgroup
([email-masked]).

   Below is a summary of publicly or commercially available sequence/structure
matching software.  I apologize in advance for any omissions or errors. Thanks
to all that replied, especially Steve Bryant, Steve Brenner, Gordon Crippen,
Vladimir Maiorov, and David Eisenberg. 

1) Brenner ([email-masked])
   plans to make software available "once it's stable"

2) Bryant ([email-masked]), Lawrence
   The Bryant threading software is available via anonymous ftp from
   ncbi.nlm.nih.gov (130.14.25.1) in the compressed tar archive
   /pub/pkb/Threading.tar.Z. 

3) Blundell, Donnelly, Eisenmenger, Johnson, Overington, Sali, Topham,
   Blundell's Composer software is available from Tripos Associates however
   the Blundell's sequence/structure software is currently not available. 

4) Crippen ([email-masked]), Maiorov ([email-masked])
   Crippen and Maiorov's contact potential software may be obtained by writing
   Vladimir Maiorov. 

5) Eisenberg ([email-masked]), Bowie, Choe, Luthy, McLachlan, Mcleod,
   Wesson, Wilmanns, Yamashita
   Academics may obtain the 3D Structures Profile software by writing David
   Eisenberg.  Commercial sites may obtain this software through Biosymm. 

6) Jones ([email-masked]), Taylor, Thornton
   plans to make it available, but not ready yet

7) Ouounis, Sander, Scharf, Schneider
   no information

8) Sippl, Casari, Floeckner, Froschauer, Gottsbacher, Hendlich, Lackner,
   Weitckus
   no information

9) Skolnick, Godzik, Kolinski
   Sknolnick's MatchMaker software will be available from Tripos Associates.

   The following excellent reviews compare and contrast the various methods
available for sequence/structure matching. 

(1) Wodak, S. J.; Rooman, M. J. Generation and testing protein folds.  Curr.
    Opinion Struct. Biol.   1993, 3, 247-259.

(2) Fetrow, J. S.; Bryant, S. H. New programs for protein tertiary structure
    prediction.  Bio/Technology   1993, 11, 479-484.

     I hope you find the above information useful.

     Sincerely,

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| Konrad Koehler              |  Computational Chemistry Group     |
| internet:  [email-masked]  |  Department of Medicinal Chemistry |
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>From [email-masked] Fri Feb 18 19:11 GMT 1994

Andy:

There are many ways you could achieve this:

1. BLAST server
2. FASTA protocol
3. Server in Heidelberg

You can obtain information on 1 & 2 by setting your gopher client to any
of the biology gophers (e.g. fly.bio.indiana.edu).

I like 3, since it not only provides the homology, but also the
secondary structure prediction.  This server is maintained by Chris
Sander's group at EMBL, Heidelberg.

To get instructions on using the server do the following:

send email to the following address with no subject field:

[email-masked]

just include the word "help" in the body of the message.

Cheers
-raman
-- 
C.S.Raman                                 [email-masked] - Internet
UNIX Programming & Administration         [email-masked] - CIS
SPARC & SGI Systems                       [email-masked] - CHPC
Department of Biochemistry                [email-masked]
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7703 Floyd Curl Dr.                       (210) 567-6623   [Tel]
San Antonio, TX 78284-7760                (210) 567-6595   [Fax]
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>From [email-masked] Mon Feb 21 16:37 GMT 1994

Hi Andy,

Standard rationale for getting 3D structures from sequence usually involve

1) database search of primary sequences (Brookhaven have some facilities 
   for this)

2) alignment of "best score" sequences (use FASTA, SOMAP etc.)

3) modelling of chunks or unknown sequence onto the 3D shapes of
   homologous proteins

4) annealing unknown coordinates to "stitch together" all the residues
   to make a final 3D model

5) refinement and minimization/dynamics

Quanta/CHARMm have , believe it or not, all of steps 1 to 5!

You can scan your structure database and get back "best hits". Use
FASTA to align multiple sequences (usually around 5 at once). Then
replace unknown coordinates bit by bit (based on the best homologous
structure/sequence). The annealing is done by CHARMm and you tweak the
refinement using rotamer libraries to place your sidechains. Then finish
off with CHARMm for the final minimization.

Let me know if you need any help in setting up your files etc. to
automate your database searching/alignments.

Richard

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>From [email-masked] Mon Feb 21 18:03 GMT 1994

Hi Andy,

I know of two commercial programs that can do what your colleague desires.
One is COMPOSER, part of SYBYL (Tripos, St. Louis, MO, USA) and the other is
HOMOLOGY, part of Insight (BioSym, San Diego, CA, USA).  COMPOSER is based on
T. Blundell's work (Eur. J. Biochem., 172:513-520 (1988)) and HOMOLOGY is 
based on J. Greer's work (J. Mol. Biol., 153:1027-1042 (1981)).

It is important to know the phylogenetic relationship among other known 3D 
proteins in order to do this type of modelling.

Good luck,

Thomas Nittoli
Dept. of Chemistry
State University of NY
Stony Brook, NY 11794-3400 USA

Phone: (516)632-7854   FAX: (516)632-7960
Internet: [email-masked]