Re: Fitting molecular structures

[Tudor Oprea <tudor -x- at -x- wucmd.wustl.edu>]

 On Wed, 26 Jan 1994, Dirk Huckriede wrote:
 >
 > 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.
 >
 >
 ------------------------------------------------------------------------------
 >  Dirk Huckriede
 >
 >  Conformational Analysis Group
 >  Gorlaeus Laboratories
 >  Leiden University
 >
 >  P.O. Box    9502                Phone : +31 71 274505
 >  2300 RA   Leiden                  Fax : +31 71 274488
 >  The  Netherlands               E-mail : dirk -x- at -x-
 rulglj.leidenuniv.nl
 >
 ------------------------------------------------------------------------------
 > "to be or nut^H^H^H -- sh^Gt, how do I delete..^?^?^? Oh No Oh
 NO^D^D^D -- How
 > do I get out of this thing anyway^C^C^C Kill it^Z^Z^Z (mumble mumble)
 > Bus error (core dumped)
 >
 ------------------------------------------------------------------------------
 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:                 =
   Lopata 510, Box 1099, One Brookings Drive          = tudor -x- at -x-
 wucmd.wustl.edu  =
   St.Louis MO 63130                                  ==========================