Makya lets you generate molecules that maximize 3D Shape and 3D Pharmacophore Similarities to a reference 3D molecule during generation.
To set up new 3D ligand-based parameters, simply click on the "3D Ligand-based" tab, then create a 3D score by clicking on the "New 3D Ligand-based +" button:
Upload a reference ligand and set an anchor
Enter the information (in the form of a SMILES or an SDF file) for 2 important molecular structures:
- your reference molecule,
- and the anchor substructure. The anchor is a subunit of the reference molecule that serves as the starting point for 3D alignment.
Note: The anchor is not mandatory for the 3D ligand-based generators. However, if you decide to include it, please remember the following important information.
IMPORTANT: This sub-unit has to be present in all the generated molecules for the 3D alignment to be done. With the Growing or Linking generators, please make sure that your exit vector contains this part somehow (in the exit vector or the building block).
Select a conformer
If you have a preferred conformer for your reference molecule, you can upload an SDF file directly.
NOTE: RDKit should be able to convert your SDF back to SMILES in order to score the generated molecules. Before uploading your file, please check that this is the case.
If you do not have a preferred conformer, or if this conformer can be generated by RDKit, you can simply enter the SMILES of your reference molecule (or use the sketcher tool by clicking on the pen icon).
Makya will automatically generate up to 10 probable conformers, sorted in ascending order of energy. You can choose the one you prefer using the arrows on top. If you want more conformer suggestions, you can click on the spinning arrows symbol. Once a conformer has been chosen, you can name it and click on the Next button.
Customize pharmacophores
You can customize pharmacophores to calculate the 3D Pharmacophore score.
Select the pharmacophore type you want to generate, using the reference molecule's 3D conformation as a template.
Adjust the weights of pharmacophores so as to indicate which are important to find in generated molecules.