The goal of this use case is to demonstrate how, starting from a given central core motif, we can generate new interesting molecules.
Step-by-step guide to the generator set-up
Step 1:
Create a new Fragment Growing generator.
Step 2:
In the Exit vectors section, draw the hinge binding motif(s) of your choice. This will be our starting fragment. For instance here we use a pyrazol amine.
Step 3:
You can then define the exit vectors, which are the groups of atoms where the reactions will take place. Here, since we want to generate new molecules with this pyrazol amine as a central scaffold, you need to define two exit vectors so as to grow your molecules from two different reactive centers.
NOTE: If you have a precise idea of the type of building blocks you want to add on your exit vectors, you can add building block constraints (physico-chemical properties, substructure constraints) in the "Building Blocks" tab.
QSAR models, APIs and scorers can be added to guide the generation. In such use case which is close to a patent busting one, a docking score would be especially appropriate and can be added in the 3D Structure based tab (available with the Makya 3D options). Alternatively, a chemical space can be used to guide the Growing generator using Tanimoto similarity to reference molecules.
Step 4:
Once the generator have been set up, just save and click on run. After several minutes the first results will pop up.
As you can see each molecule contains the central motif (pyrazol amine) and two commercial building blocks have been added in the expected positions.