How do I perform a conformational search on a set of ligands and constrain a substructure or torsion that is conserved in each input structure ?

You will need to specify your torsion or substructure with a SMARTS pattern, and then use the Substructure facility to implement the constraint, as using the Constraints tab doesn't permit you to do this. Follow these steps.

1. Select the input ligands in the Project Table.
2. Include the first structure in the Workspace, and select the atoms that constitute the substructure or torsion that you want to constrain. They should be highlighted with yellow markers.
3. Open the Conformational Search panel (Applications → MacroModel → Conformational Search).
4. Make any desired selections in the Potential, Mini, and CSearch tabs.
5. In the Substructure tab, first create a new shell by clicking the New button.
6. Enter the substructure or torsion atom information into the "Additional atoms for shell" text box using the Atom Selection dialog box.
   In Suite 2012, click the green "+" button or blue arrow button, then click Select to open the Atom Selection dialog box; in earlier suites, click the Select button. In the Substructure tab, select SMARTS and click the "Get from Selection" button. Click Add, then click OK. The SMARTS pattern of the selected substructure from the Workspace is entered into the text box.
7. Copy the SMARTS pattern from this text box (press CTRL+A CTRL+C).
8. In the "Freely moving atoms" text box, type the text 'not ', then paste (CTRL+V) the SMARTS pattern you copied into the text box. This defines the ASL expression for the freely moving atoms to be everything but the atoms defined by the SMARTS pattern.
   
   You have now indicated that the substructure atoms will be constrained, and that all additional atoms will be free to move during the search.
9. Important: Select the "Write ASL formatted .sbc files" option. This ensures that that the constraints will be applied correctly to each individual input ligand.
10. At the top of the Conformational Search panel, choose Project table from the "Use structures from" option menu.
11. Click the Start button to set up the job and run the constrained conformation search.

You can use the resulting job files as a template for other, similar searches, which can be run from the command line.

Keywords: constrain, restrain, ASL, csearch, Maestro, MacroModel

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