Subject: A summary on Flexible Docking Software

From: Lim Teck Sin <[email-masked]>
Date: Thu, 14 Sep 1995 14:36:08 +0800 (SST)

Hi,

  I asked about the availablility of flexible docking software recently. 
Thanks to those who replied on CCEMD, DOCK, BIOSYM and SCULPT packages.
(see below)  However, I am wondering if there are anymore software (ex: 
Tripos?) that have/will have such functionality?  I will post another 
summary if I receive more emails on this subject.  Thanks!!!

best regards - teck sin

----------------------------start of summary-----------------------------
Date: Mon, 11 Sep 1995 10:29:45 -0700 (PDT)
From: judson richard s <[email-masked]>
To: Lim Teck Sin <[email-masked]>
Subject: Re: CCL:Flexible docking software

We have started handing out copies of our general purpose MD code CCEMD
which does flexible docking of ligands. Getting the code requires signing
a license - at the moment, the only requirement is that it only be used for
non-proprietary, non-commercial purposes. I have a users' manual and 
copies of a couple of papers that I can send if you will give me an address.

> | Richard Judson                              				
> | Center for Computational Engineering, MS 9214       	
> | Sandia National Laboratories                        	
> | Livermore, CA 94551-0969
> | (510)294-1438
> | (510)294-2234 (FAX)
> | email: [email-masked]

-----------------------------------------------------------------------
Date: Mon, 11 Sep 1995 10:36:23 -0700 (PDT)
From: "Dr. David N. Haney" <[email-masked]>
To: Lim Teck Sin <[email-masked]>
Cc: "Dr. David N. Haney" <[email-masked]>
Subject: Re: CCL:Flexible docking software

I have proposed work that will modify Kuntz's DOCK with modal methods
to add flexibility.  We expect this work to begin soon, but software
would not be completed for at least a year or two.

**************  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]  ***************

---------------------------------------------------------------------
Date: Mon, 11 Sep 1995 15:46:26 -0400 (EDT)
From: Jie Yuan <[email-masked]>
To: Lim Teck Sin <[email-masked]>
Subject: Re: CCL:Flexible docking software > Just read the newsletter 
from Biosym.  

The to-be-released Biosym package will have a molecular mechanics/grid 
method implemented in Discover that treats the bulk of the receptor as 
rigid but treats the critical binding site and ligand with molucular      
mechanics (therefore 'flexible', IMHO).  I have not used this   
product yet.  You might want to look at their WWW pages for     
more info:  http://www.biosym.com/

> -- Jie Yuan, PhD - Pharmacology & Cell Biophysics - U. Cincinnati --
> -- Phone: 513-558-2352 -- Fax: x-1169 --  Email: [email-masked]  --
> -- P.O. Box 670575, 231 Bethesda Ave., Cincinnati, OH 45267-0575  --
> -- http://www.uc.edu/~yuanj

----------------------------------------------------------------
Date: Tue, 12 Sep 1995 18:40:56 +0200
From: "Klaus J.W.May" <[email-masked]>
To: Lim Teck Sin <[email-masked]>
Subject: Re: CCL:Flexible docking software

There is a Software called SCULPT. It might be of help to your work. There
are several questions open.
What is your understanding of "docking software"? Do you want a automatic
procedure which finds also docking sites on a given receptor? Or are you
looking for tools which give you answers for possible ligands in a given
site?
(note from TeckSin: I am looking for tools that can autodock sites too.)

Anyhow - SCULPT is a "interactive package". It does REALTIME minimizations
of given systems with user definable degrees of restrictions to flexibility
and interactive "pull forces" to given atoms or sets of atoms/residues. Not
always one wants to have the full system fully flexible. For docking
studies, f.i. there is a function called "tug". It keeps the defined set of
atoms rigid with respect to themselves. But they start to minimize as soon
as some "outer" force is applied to them. One can think of a physical
model, which deformes, while squeezed through a hole.
but - what do I try to explain... You can have a demoversion free of cost.
Downloadable via internet. It runs on SGI. A brandnew Powermac version is
available soon.  look at the homepage    http://www.intsim.com/~isigen
and learn more about SCULPT
Good luck!

Klaus J.W. May                   e-mail:          [email-masked]
May & Partner                   Phone/Fax:       xx49-(89) 333 569
SciTech Consult                  Mobile national: 0171-80 80 900       
Mandlstr. 15                      international: xx49-1712-80 80 
900       
D - 80802 Munich GERMANY

---------------------------------------------------------------------
[email-masked]>
Newsgroups: biosym.chemistry
Subject: CCL:Flexible docking software

In the 950 release from Biosym/MSI scheduled for next month,
there is a new product named Affinity which does flexible docking.
Both the ligand and receptor are flexible. It is an energy-based
method and it combines the merits of Monte Carlo, minimization and dyanmics.
It also uses the molecular mechanics/grid method of Luty et al.
(JCC, 16, 454, 1995) to speed up the calculation and to include
implicit solvation model of Stouten et al. (Mol. Simulations,
10, 97, 1993). For more infomation, please contact your local
Biosym/MSI sales office.

Congxin Liang
Biosym/MSI

--------------------------------------------------------------------
Date: Wed, 13 Sep 1995 12:21:57 -0800
From: "Mark C. Surles" <[email-masked]>
To: Lim Teck Sin <[email-masked]>
Cc: [email-masked]
Subject: Re: CCL:Flexible docking software

Sculpt from Interactive Simulations provides both flexible receptor and
ligand during real-time, user-guided docking.  Flexibility is a function of
energy minimization.
See the Flavin/Flavodoxin, HIV protease, and Beta lactamase examples in the
demos.  Demos are available via the WWW at http://www.intsim.com/~isigen or
end email to [email-masked].

Mark Surles
Interactive Simulations, Inc.      Phone: (619) 658-9462
5330 Carroll Canyon Road           FAX:   (619) 658-9463
Suite 203                          Email: [email-masked]
San Diego, CA  92121               URL:   http://www.intsim.com/~isigen

------------------------------------------------------------------------
Date: Wed, 13 Sep 1995 18:12:49 -0400
From: Nick Hodge <[email-masked]>
To: [email-masked]
Subject: CCL:Flexible docking software

A brief expansion on Congxin's note regarding flexible docking

As indicated, the method was developed at DuPont Merck and employs
molecular dynamics to 'fly' a ligand into the active site of an enzyme. The
active site is flexible and represented explicitly, an intermediate region
of the enzyme is restrained, and a grid represents the rest of the enzyme.
An atom-based solvation term is added (Stouten et al. Mol. Simulations, 10,
97, 1993). The initial implementation (Luty et al., JCC, 16, 454, 1995) was
able to reproduce the crystallographic orientation of benzamidine in
trypsin rapidly and accurately, starting from random orientations outside
of the active site; similarly, leucine hydroxamic acid finds its way into
the crystallographically observed orientation in thermolysin (Wasserman and
Hodge, Proteins: Structure, Function and Genetics, in press).
In neither case do we attempt to correlate energies with the experimentally
observed conformations, but preliminary analysis suggests that some
correlation is possible. The successful extension to thermolysin and a more
flexible inhibitor is also encouraging. However, the method has to be
considered preliminary and in need of extensive testing and improvement.
The Biosym implementation includes a Monte Carlo conformation/location
generator and minimization to find optimum docked sites, as well the
Discover 3.0 environment and cvff or cff91 forcefields; Amber is still
being used as well at DuPont Merck. The results with cvff are similar,
although not identical, to Amber in the limited comparisons that have 
been run.
We are very interested in comments, suggestions, enhancements etc. to the
method. We should also make clear that it is an extension of earlier and
continuing docking protocols of Goodford, Olson, Kuntz, Bohm etc. and
relies on many of their observations and ideas.

--------------------------end of summary-------------------------------