Subject: Re: CCL:Questions about InsightII and Quanta

From: Rita Wilby <rwilby:at:accelrys.com>
Date: Wed, 20 Oct 2004 11:29:30 -0700

Hello Tom,

Thank you for your question on Insight II and QUANTA, which are now 
provided by Accelrys.

Insight II, originally from Biosym, is primarily a macromolecular modeling 
application. Insight II functionality includes simulations, homology 
modeling, protein structure analysis, de novo design, and docking. 
Specific modules within Insight II are comprehensively listed on our 
website:
http://www.accelrys.com/insight/

QUANTA, originally from MSI, is primarily a macromolecular structure 
determination tool for X-ray crystallographers. Additional functionality 
includes simulations, homology modeling, protein structure analysis, and 
de novo design. 
http://www.accelrys.com/quanta/

Insight II has two de novo design tools, namely MCSS and Ludi. Each method 
has a different approach to the placement of fragments for de novo design. 

MCSS was developed in Martin Karplus' laboratory at Harvard and uses 
CHARMm-based energies to explore and rank fragment binding sites starting 
with a large number of potential locations for selected fragments on of 
ligands. More information on MCSS is available in the originators' 
publications and Accelrys documentation:
1. Miranker, A., Karplus, M. 1991. Functionality maps of binding sites: a 
multiple copy simultaneous search method. Proteins: Struc. Func. Gen, 
11:29-34 
2. Caflisch, A., Miranker, A., Karplus, M. 1993. Multiple copy 
simultaneous search and construction of ligands in binding sites: 
application to inhibitors of HIV-1 aspartic proteinase. J. Med. Chem. 
36:2142-67
3. http://www.accelrys.com/insight/mcss.html
4. http://www.accelrys.com/doc/pdf/mcss2K.pdf

Ludi was developed by Hans-Joachim Boehm at BASF. Ludi places fragments 
according to matches with interaction sites, which are then prioritised by 
its internal scoring function. The pre-computed interaction sites may be 
derived from an alignment of known active ligands or from a rules-based 
complementary image of a macromolecular binding site. Ludi functionality 
is documented in 
1. H.-J. Böhm,?The Computer Program Ludi:A New Method for the De Novo 
Design of Enzyme Inhibitors,? J. Comp. Aided Molec. Design, 6, 61-78, 
1992.
2. H-J. Böhm,?The Development of a Simple Empirical Scoring Function to 
Estimate the Binding Constant for a Protein Ligand Complex of Known 
Three-dimensional Structure?, J. Comp. Aided Molec.
Design, 8, 243-356, 1994.
3. H.-J. Böhm,?Ludi: Rule-based Automatic Design of New Substituents for 
Enzyme Inhibitor Leads?, J. Comp. Aided Molec. Design, 6, 593-606, 1992.
Boehm, H.-J. "Towards the automatic design of synthetically accessible 
protein ligands: peptides, amides, and peptidomimetics," J. Comput.- Aided 
Molec. Des., 1996, 10, 265-272. 
http://www.accelrys.com/insight/ludi.html
http://www.accelrys.com/doc/pdf/ligand2K.pdf

A detailed comparative analysis of Ludi and MCSS is available if you are 
interested.

MCSS/Hook was developed by Rod Hubbard's laboratory in University of York. 
MCSS/Hook, available only in QUANTA, includes MCSS functionality and 
extends MCSS by connecting selected fragments that are already favorably 
placed. More information on MCSS/Hook is available from:
1. M.B. Eisen, D.C. Wiley, M. Karplus and R.E. Hubbard "HOOK: A program 
for finding novel molecular architectures that satisfy the chemical and 
steric requirements of a macromolecule binding site." Proteins Structure, 
Function and Genetics, 1994, 19, 199-221.
2. http://www.accelrys.com/quanta/mcss_hook.html
3. http://www.accelrys.com/doc/life/quanta2K/pdf/mcss-hook_book.pdf

Ludi and MCSS/Hook have parallel functionalities also. Ludi will connect 
two or three separate fragments in a site if it can find a fragment that 
matches available link sites, similar to Hook.

We will be happy to discuss any or all of these questions with you 
off-line, to avoid spamming CCL.

Regards,
Rita

Marguerita Lim-Wilby, B.Pharm., Ph.D.
Product Manager, Structure-Based Design
Accelrys Inc., http://www.accelrys.com

Tel: (858) 799-5486
Cell: (858) 344-0156
Fax: (928) 752-8479
email: rwilby:at:accelrys.com

"Tom Cao" <tomc1234:at:hotmail.com> 
Sent by: "Computational Chemistry List" <chemistry-request:at:ccl.net>
10/19/2004 10:59 AM

To
chemistry:at:ccl.net
cc

Subject
CCL:Questions about InsightII and Quanta

Dear All,

I have a couple of questions regarding InsightII and Quanta made by MSI. 
Thank you in advance for your help.

1) Both of the InsightII and Quanta are molecular modeling software, 
what's 
the real difference between them? for example force field enigen ...? 
What's 
the advantage of each of them?

2) InsightII has Ludi, Quanta has MCSS and HOOK, what's the advantage 
between these two de novo design methods?

Thanks again for your help.

Sincerely

Tom

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