Chemical Space Docking®

The workflow starts with the docking of the building blocks that are used in the creation of the selected Chemical Space.
In this step, you have the opportunity to apply pharmacophore constraints at your defined binding site. This will guide the placement of synthons (the initial starting fragments for compounds) and identify those capable of forming desired interactions with the target.

Once the synthons have been docked, you can examine the produced poses with the visual support provided by SeeSAR. Each synthon is equipped with a marker indicating its extension direction, referred to as a 'linker atom', thereby simplifying the evaluation process.

The chosen candidates then move forward to the next phase of the workflow: the extension stage.

After the anchoring phase, selected synthons expand into drug-like compounds during the extension stage. Here, the initial fragments are combined with other building blocks following chemical reaction rules of the Chemical Space. Only compounds that can be synthesized are created and assessed for their interactions at the binding site.
The setup within SeeSAR swiftly processes the docking of the extended compounds with precision to ensure they mirror the binding mode of the synthon starting point. This approach is several times faster than conventional docking methods and guarantees that the evolved compounds match the orientation of your starting fragment.

Again, you as a user can guide the process with pharmacophore constraints to introduce additional interaction patterns into the results.

Once the calculations have finished, you are presented with results of two kinds: Compounds with a linker and those without a linker. Compounds without a linker are final molecules that can be ordered or synthesized. Compounds still containing a linker require an additional extension run that will lead to final molecules.