Macrocyclization Settings Dialog Box

Choose structure and spacers for macrocyclization of a ligand in the Ligand Designer.

To open this dialog box, click the Settings button in the Modify lead banner opened by the Ligand Designer Panel.

  • Features
  • Additional Resources

Macrocyclization Settings Dialog Box Features

Structure options

Choose the structure for input to the macrocyclization.

  • Use Protein-Ligand Complex—use the protein to help guide the macrocyclization of the ligand. The linker is built to accommodate the receptor and any resulting conformations that are highly strained are eliminated. Use of the protein is an order of magnitude slower than just using the ligand.

  • Use Ligand Only—Use the ligand without the protein. This can result in clashes with the protein, which can be eliminated later, but it is much faster.

Spacers check boxes

Select the spacers to use to form the link between attachment points on the ligand. If you want the PEG and Amide linkers to be attached by either end to the link, select both fragments.

  • C—use methylene linkers

  • PEG1—use ethylene glycol as a linker (SMARTS pattern CCO), with the terminal carbon attached to the existing attachment point on the ligand or the previous linker, and the oxygen as the next attachment point. Put another way, the growth direction is from C to O.

  • PEG2—use ethylene glycol as a linker (SMARTS pattern OCC), with the oxygen attached to the existing attachment point on the ligand or the previous linker, and the terminal carbon as the next attachment point. Put another way, the growth direction is from O to C.

  • Amide1—use an amide linker, SMARTS pattern NC(=O), with the nitrogen attached to the existing attachment point on the ligand or the previous linker, and the carbon as the next attachment point. Put another way, the growth direction is from N to C.

  • Amide2— use an amide linker, SMARTS pattern C(=O)N, with the carbon attached to the existing attachment point on the ligand or the previous linker, and the nitrogen as the next attachment point. Put another way, the growth direction is from C to N.

  • Use custom spacers—use custom spacers, specified as SMARTS patterns in the text box. Enter a custom spacer and click the add (+) button to add it as a spacer, and repeat for each custom spacer. These spacers are listed below, with an X button to remove them. The first atom in the SMARTS pattern is attached to the link, the last atom becomes the next attachment point in the link.

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