Subject: Fitting molecular structures

From: [email-masked] (Dirk Huckriede)
Date: Wed, 26 Jan 94 10:57:44 -0800

Hello all,

I have two sets of cartesian coordinates. They both contain a common part, say
a  five membered ring. The orientation of each molecule is different. 
I want both molecules to have the same orientation based on the common part. 
Does anyone of you out there tried to solve this ? 

Any help will be appreciated.

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From: Tudor Oprea <[email-masked]>
Date: Wed, 26 Jan 1994 10:38:27 -0600 (CST)

> Any help will be appreciated.
First put this line in your .cshrc - it will help you get OUT
limit coredumpsize 0 kbytes
;-)

Second, it depends on the type of investigation you are doing. If a geometric fit
satisfies you, just match the atoms you think correspond (any modeling program will
do that). If you have a pharmacophore hypothesis, try to fit the common pharmaco-
phoric elements, regardless of the actual structural fit. This should give you
an idea of how the two structures fit in the same binding site. 
If you can go sophisticated, use the field-fit procedure in Sybyl, that would allow
you to fit one ligand in the steric and electrostatic (or in either one of them)
individually. I advise you relax the resulting field-fitted structure using 
steepest-descent for ~100 steps, then conjugate gradient (to go to the nearest pit).
Clark et al, Tetrahedron Comput Methodol 1990 3:47 for field fit
It is possible to use the approach of Perkins & Dean (JCAMD 1993 7:155) which will
allow you to use simulated annealing & cluster analysis to get the best match.
RECEPTOR & Constrained systematic search are available in Sybyl - use that in
conjunction with the Active Analog Approach
Dammkoehler et al, JCAMD 1989 3:3
If you want to go automatic, use DISCO (from Yvonne Martin, Abbott)
see Trends in Molecular Modelling '92 (ESCOM, Leiden - your town! 1993), 
ed. CG Wermuth, for Martin et al, pp 20 - and references therein.
Other procedures that you may use are: Grid (from Peter Goodford) and Cosmic
(from Andy Vinter) - both probe the molecules with H+, HO- and H20 and 
superpose fields, rather than structures.
Contact me if you have any questions...

--Tudor

                                                     ==========================
  Tudor-Ionel Oprea                                  = Tel. (1-314) 935 4672  =
  Research Associate                                 = Fax. (1-314) 935 4979  =
  Washington University Center for Molecular Design  = Email:                 =
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