Subject: Re: CCL:Summary: flexible docking program

From: [email-masked] (Pieter Stouten)
Date: Tue, 25 Jan 2000 10:35:52 +0100

I am pleased to be credited with the attached mail on Affinity. 
However, it was not me. This is what I had written:

> If you have access to MSI software, you can use Affinity, which will 
> keep part of your enzyme rigid, part of it flexible but constrained
> to starting (e.g. crystallographic) coordinates and part of it
> completely flexible. It is basically an MD program (so it is not so
> useful for large numbers of ligands), but expressing the rigid part
> of the enzyme on a grid leads to dramatic speed ups. Affinity also
> has a continuum solvation model, but that is not fully reliable.
> However, if one does not study fully unconstrained proteins, the
> solvation term may help.
>
> The MSI implementation of Affinity was a joint collaboration between 
> Ciongxin Liang (then with Biosym, now with Sugen) and the DuPont
> Merck CADD group (Brock Luty, now at Agouron; me, now at P&U; and
> Zelda Wasserman). Please let me know if you are interested in the 
> papers describing that work.

Ciao,

Pieter

______________________________ Reply Separator _________________________________

Date: Mon, 24 Jan 2000 09:55:33 +0100 
From: [email-masked] (Pieter Stouten) 

You might want to look at Affinity from MSI (URL 
http://www.msi.com/life/products/insight/modules/affinity.html).  It is an 
automatic docking module for Insight II that incorporates Monte Carlo and 
simulated annealing methods to place a ligand within a receptor.  The 
method is designed so that after the Monte Carlo phase the receptor within 
the defined binding site is flexible by default.  In other words, all you 
have to do is define the extent of the binding site.  Every receptor atom 
within that region is flexible and free to move. 

Recent publications using Affinity are: 

1.  Kurinov, I. V., Myers, D. E., Irvin, J. D., Uckun, F. M. 1999. X-ray 
crystallographic analysis of the structural basis for the interactions of 
pokeweed antiviral protein with its active site inhibitor and ribosomal 
RNA substrate analogs. Prot. Sci. 8:1765-72

2.  Read, M. A., Wood, A. A., Harrison, J. R., Gowan, S. M., Kelland, L. 
R., et al. 1999. Molecular Modeling Studies on G-Quadruplex Complexes of 
Telomerase Inhibitors: Structure-Activity Relationships. J. Med. Chem. San 
Diego, CA 92121