Tutorial 4: 3D Substructure Search

 

Objectives

 

•	To draw a chemical fragment (substructure).

•	To select only those entries which adopt a particular conformation.

•	To tabulate some parameters involving derived objects (centroids, planes).

 

Steps Required

 

•	Draw the fragment.

•	Define centroids and planes.

•	Define distances between the centroids, and angles between the planes.

•	Define a torsion angle and specify that it must lie in a certain range.

•	Run the search.

•	Save the file of geometrical parameters.

 

The Example

 

•	The tutorial explains how to search for the following fragment:

where the two central carbons are acyclic (not part of a ring) and are bonded to 1 or 2 hydrogen
atoms. The two phenyl groups will be required to be cis (i.e. Cring-C-C-Cring torsion angle
between –90 and +90 degrees). The following parameters will be saved:

•	Distance between the centroids of the phenyl rings.

•	Angle between the planes of the phenyl rings.

 

Menu Commands Required

 

1.	Start ConQuest and hit the Draw button to open the drawing window.

2.	Draw the basic fragment.

•	Use the aromatic bond type for the ring bonds, not alternate double-single (you will get the correct bond types automatically if you select the rings from the ring template area at the bottom left-hand corner of the Draw window):

3.	Specify the central C atoms to be acyclic.

•	Select Atoms from the top-level menu, Cyclicity from the pull-down menu, and Acyclic from the next menu.

•	Click on the two central carbon atoms:

 

•	Hit Done in the Select Atoms pop-up.

 

4.	Specify the number of attached hydrogens.

•	Select Atoms from the top-level menu, Hydrogens from the next menu, and Other... from the third menu.

•	Type 1,2 into the Hydrogen Count box and hit OK.

•	Click on the two central carbon atoms:

•

Hit Done.

 

5.	Define the centroids of the phenyl rings.

•	Click on the ADD 3D button.

•	Click on all six atoms of one of the phenyl rings and hit the Define button next to the word Centroid. This defines the centroid of the ring (named, by default, CENT1):

•	Similarly, define the centroid of the other ring (named, by default, CENT2).

 

6.	Define the ring planes in a similar way.

•	Click on the six atoms of one of the rings and hit the Define button next to the word Plane. By default, the plane is called PLN1.

•	Repeat for the second ring (named, by default, PLN2).

 

7.	Define the distance between the centroids and the angle between the planes.

•	Click on the names of the two centroids, CENT1 and CENT2, in the box headed Defined Objects:

 

•	Then hit the Define button next to the word Distance. This specifies a parameter, DIST1, which is the distance between the two ring centroids.

•	Similarly, click on PLN1 and PLN2 and Define the angle between these planes.

 

8.	Constrain the search so that it will only find structures in which the phenyl groups are cis.

•	Click on the four atoms defining the conformation around the central C-C bond:

 

•	Define the C-C-C-C torsion angle by hitting the Define button next to the word Torsion.

•	Hit the Options... button.

•	Type the required limits (From –90 to 90) into the 3D Limits and Options window. The specified torsion angle range is displayed graphically:

 

•	Hit OK in this window and then Done in the Geometric Parameters window.

 

9.	Run the search.

•	Hit Search, set the filters R factor <= 0.1, Not disordered, No errors and Not polymeric, and then hit Start Search.

•	View some of the hits in the 3D visualiser to confirm that the search is only finding structures in which the phenyl rings are cis.

•	Use the arrows on either side of the boxes labelled Param and Objects to control whether or not distances, angles, centroid and planes are displayed.

 

•	A file of the parameters you have defined can be saved by selecting File from the top-level menu, then Export Parameters and Data from the pull-down menu.

 

This ends the tutorial.