Subject: Summary:protein xray software

From: Chris Murray <[email-masked]>
Date: Mon, 13 Mar 1995 14:35:35 +0000

Dear all,

Here is the summary of responses I received from my question concerning the
incorporation of more crystallographic information when using structure based
drug design. I knew about the Biosym software which is nice in as far as it
goes but there seems to be scope for more interesting integration.

with thanks to all those who responded

Chris

My original question:

The design of inhibitors to fit crystallographically determined protein
structures often seems to assume that the structures are fixed. However there
should be quite alot of information in the isotropic thermal parameters and the
original diffraction data which could guide the designer about where to focus
his/her designs in the first place. It ought to be possible also to represent
this information graphically. Does anybody know of any software that does this?

I will summarise if there is any interest.

Chris Murray
Proteus Molecular Design Ltd
UK

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>From carlos%extreme.bio.cornell.edu%cornellc.cit.cornell.edu@uknet Mon Feb 27
18:18:20 1995
Date: Mon, 27 Feb 95 10:21:48 -0500
From: [email-masked] (Carlos Faerman)
To: Chris Murray <cwm>
Subject: Re: CCL:protein xray software
Status: OR

Hello Chris,

In answer to your question:
1) There is a program InsightII by Biosym that colors the protein according
to the B-factors. It gives a rough idea of the areas which are poorly (greatly)
defined. It is quite easy to use.
Please let me know whether this is what you had asked
Best regards
Carlos

Thanks
Carlos H. Faerman
[email-masked]

>From chemistry%dreamon.oxmol.co.uk@uknet Mon Feb 27 18:18:22 1995
Date: Mon, 27 Feb 95 15:55:15 GMT
To: Chris Murray <cwm>
From: [email-masked] (Chemistry list)
Subject: Re: CCL:protein xray software
Status: OR

SH

TRY ORTEP

SURVIVING

>
>The design of inhibitors to fit crystallographically determined protein
>structures often seems to assume that the structures are fixed. However there
>should be quite alot of information in the isotropic thermal parameters and
the
>original diffraction data which could guide the designer about where to focus
>his/her designs in the first place. It ought to be possible also to represent
>this information graphically. Does anybody know of any software that does
this?
>
>I will summarise if there is any interest.
>
>Chris Murray
>Proteus Molecular Design Ltd
>UK
>
>
>-------This is added Automatically by the Software--------
>-- Original Sender Envelope Address: [email-masked]
>-- Original Sender From: Address: [email-masked]
>[email-masked] -- everyone     | [email-masked] -- coordinator
>[email-masked]: HELP CHEMISTRY  | Gopher: www.ccl.net 73
>Anon. ftp www.ccl.net     | [email-masked] -- archive search
>http://www.ccl.net/chemistry.html |     for info send: HELP SEARCH to MAILSERV
>
>

>From haney%netcom.com@uknet Mon Feb 27 18:18:28 1995
From: [email-masked] (Dr. David N. Haney)
Subject: Re: CCL:protein xray software
To: cwm (Chris Murray)
Date: Mon, 27 Feb 1995 08:20:28 -0800 (PST)
Feb 27, 95 02:06:54 pm
X-Mailer: ELM [version 2.4 PL23]
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Status: OR

Chris:

I am also interested in this area and I would appreciate a summary of the info
you receive.

> The design of inhibitors to fit crystallographically determined protein
> structures often seems to assume that the structures are fixed. However there
> should be quite alot of information in the isotropic thermal parameters and
the
> original diffraction data which could guide the designer about where to focus
> his/her designs in the first place. It ought to be possible also to represent
> this information graphically. Does anybody know of any software that does
this?

--

        **************  David N. Haney, Ph.D.    ****************
        *  Haney Associates               Phone - 619-566-1127  *
        *  12010 Medoc Ln.                                      *
        *  San Diego, CA 92131            Fax - 619-586-1481    *
        **************  Email - [email-masked]  ***************

>From marvin%iris131.biosym.com@uknet Mon Feb 27 18:18:35 1995
Date: Mon, 27 Feb 1995 08:56:50 -0800
From: [email-masked] (Marvin Waldman)
To: cwm
Subject: RE:protein xray software
Status: OR

Hi Chris,
Using InsightII, it is possible to color code the VDW or Connolly surface
of a molecule based on the Temperature factor information stored in
the PDB file.  Here is an example of the appropriate commands for
Crambin:

m:Surface Molecule Create VDW CRN Dot 1 0 Medium -Context
m:Color Molecule Surface CRN Specified Temperature_Factor TEMP_FACTOR_SPECTRM

Regards,

Marvin Waldman, Ph.D.
Manager, Rational Drug Design
Biosym Technologies, Inc.
e-mail: [email-masked]

>From vijay%jellyfish.chem.wesleyan.edu@uknet Mon Feb 27 18:18:36 1995
Date: Mon, 27 Feb 95 11:33:43 -0500
From: "S." Vijayakumar <[email-masked]>
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To: Chris Murray <cwm>
Subject: Re: CCL:protein xray software
Status: OR

	Very true! They reflect the local flexibility of the
different residues, which when taken into consideration can make a
difference in the design of potential drugs. The anisotropic thermal
factors where available could be even more helpful.  We use a
software called MD Toolchest here at Wesleyan, which is a collection
of several different programs that interact with each other to
analyze and produce graphical output.

	For a graphical presentation, we simply represent the
thermal-factors as spheres (isotropic) or ellipsoids (anisotropic) of
appropriate radii and project the molecule on to a plane based on the
orientation specified by the user. If necessary one can select the
residues comprising the active site alone.
	Hope that helps...

Vijay

*************************************************************
S. Vijayakumar, Ph. D., DCA
Department of Chemistry,  Wesleyan University, Middletown, CT 06459
Voice:	(203) 685-2777 / 3213		Fax:	(203) 685-2211
email:	[email-masked]
*************************************************************

>From shoba%atp.biochem.usyd.edu.au@uknet Tue Feb 28 09:19:40 1995
Sender: shoba <[email-masked]>
From: Shoba Ranganathan <[email-masked]>
To: Chris Murray <cwm>
Date: Tue, 28 Feb 1995 07:57:17 +0000
Subject: Re: CCL:protein xray software
Reply-To: [email-masked]
Status: OR

I would be interested in such software information -
if you are not summarizing, could you kindly forward to
me any replies that you get?

Thank you.

Shoba

>From d.winkler%chem.csiro.au@uknet Tue Feb 28 09:19:43 1995
Date: Tue, 28 Feb 95 09:49:47 EST
From: "Dr." Dave Winkler <[email-masked]>
Subject: Re: CCL:protein xray software
To: Chris Murray <cwm>
Status: OR

>The design of inhibitors to fit crystallographically determined protein
>structures often seems to assume that the structures are fixed. However there
>should be quite alot of information in the isotropic thermal parameters and
the
>original diffraction data which could guide the designer about where to focus
>his/her designs in the first place. It ought to be possible also to represent
>this information graphically. Does anybody know of any software that does
this?

This is a clever thought.

>I will summarise if there is any interest.
>
Please do. (or send me a copy at any rate)

Cheers,

Dave
__________________________________________________________________________

   Dr. David A. Winkler                        Voice: 61-3-542-2244
   Principal Research Scientist                Fax:   61-3-543-8160
   CSIRO Division of Chemicals and Polymers
   Private Bag 10                              CSIRO: http://www.csiro.au
   Clayton, Australia.

>From ng%tesla.mbi.ucla.edu@uknet Tue Feb 28 09:20:40 1995
Date: Mon, 27 Feb 95 17:58:55 -0800
From: [email-masked] (Ng)
To: cwm
Subject: Re: CCL:protein xray software
Status: OR

   I'd like to hear a summary of information you receive or if you uncover
any interesting references.

Thank you!

Ho Leung Ng
[email-masked]

>From martin%cmda.abbott.com@uknet Wed Mar  1 09:08:07 1995
Date: Tue, 28 Feb 1995 14:41:19 -0600 (CST)
From: [email-masked]
Subject: Re: CCL:protein xray software
To: cwm
Status: OR

I certainly am interested in the response.

Yvonne Martin
Abbott Laboratories

>From koehler%irbm.it@uknet Mon Mar  6 00:13:10 1995
Date: Sun, 5 Mar 1995 17:13:52 +0100 (WET)
From: "Konrad, IRBM Chemistry, +39-6-91093606" <[email-masked]>
To: cwm
Cc: [email-masked]
Subject: RE: CCL:protein xray software
Status: OR

Chris:

    It is possible to color code atoms according to crystallographic tempera-
ture factors in Insight/Discover.  As far as I can figure out, there is no
corresponding functionality in Sybyl.  I have just posted a message to the
Sybyl newsgroup asking if anyone knew a way of doing this in Sybyl.

    Related to this issue, I just ran across a thought-provoking paper
by Lumry[1] who argued that proteins should be classified according to internal
structures defined by low temperature factors rather than the usual secondary
structural elements.  He described these low temperature factor networks of
atoms as "knots".   The extention of this idea to protein-ligand complexes is
obvious.  While I find Lumry's rabid anti-reductionist view point a little
hard to take, I found the paper interesting nonetheless.

[1] Lumry, R. The new paradigm for protein research. In "Protein - Solvent
    Interactions"; Gregory, R. B., Ed.; Marcel Dekker: New York, 1995; pp
    1-141.

    I would appreciate receiving a summary of the responses to your posting.
Likewise, if you have any references of the use of temperature factors in
drug design, I would appreciate receiving them as well.

    Ciao,

Konrad

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