Application: Local Chemical Space Exploration¶

This workflow uses inpainting to explore structural variants around a known reference molecule while keeping the rest of the 3D scaffold fixed. It is useful when you want to probe a local neighborhood of chemical space rather than generate fully unconstrained molecules.

When to Use This¶

Tip

Use local exploration when you want to:

preserve a known active or synthetically meaningful scaffold,
vary only a specific substituent, ring system, or side chain,
compare how controlled structural edits affect downstream properties.

In the MolCraftDiffusion paper, this idea is used to explore variants around a reference ligand while retaining the chemically important core.

Conceptual Workflow¶

[Reference XYZ structure]
          |
          v
[Select atoms to regenerate]
          |
          v
  [Inpainting: fix scaffold,
   redraw selected region]
          |
          v
[Compare variants: diversity,
 validity, downstream properties]

The key idea is not to search all of chemical space. Instead, you stay near a known structure and deliberately vary only the region that matters for your design question.

Why This Matters¶

Note

Local exploration is often the right mode when a full generative search is too broad. It helps answer questions such as:

What happens if I replace one substituent while preserving the rest of the molecule?
How much structural diversity can I obtain around a validated scaffold?
Which local edits improve the property of interest without moving too far from a known design?