Spotlight on SpaceMACS: Precision Substructure Mining at Scale
In the search for the next lead candidate, medicinal chemists often focus on specific structural motifs while requiring absolute synthetic accessibility. This month, we focus on SpaceMACS, our specialized algorithm designed to perform rapid substructure searches across trillions of compounds within massive Chemical Spaces.
How Does SpaceMACS Accelerate Discovery?
- Identifies compounds containing your specific motifs in a flash.
- Retrieves up to millions of relevant results from combinatorial libraries.
- Provides the “next best” molecules if an exact match is not available.
- Delivers results that are synthesizable or purchasable by design.
The Advantage of Motif Driven Exploration
Standard virtual screening often struggles with the sheer volume of modern chemical libraries. SpaceMACS overcomes these limitations by utilizing the combinatorial architecture of the space rather than relying on exhaustive enumeration. It serves as the engine for the Motif Matcher mode in infiniSee, allowing researchers to navigate billions of molecules on standard hardware without the need for high performance computing clusters.
A Deep Dive into Substructure Mining Logic
Developed in collaboration with the University of Hamburg, the SpaceMACS algorithm is optimized for maximum common substructure searching. This approach provides a versatile toolkit for several key drug discovery scenarios:
- Fragment-Based Projects: Efficiently find follow up candidates that maintain the motif of a confirmed binder.
- Pharmacophore Expansion: Use QSAR suggested pharmacophores as substructures to identify decorated analogs.
- Novel Lead Discovery: Uncover unexpected structural directions that may be hidden within trillions of possibilities.
- High Quality AI Inputs: Generate massive, synthetically relevant datasets to feed machine learning and AI methods.
Versatile Approach to Extract Related Structures
As a tool, SpaceMACS can be used in different ways to retrieve relevant chemistry. One of those methods is the Maximum Common Substructure (MCS) search, which starts from a query structure (or motif) and then looks for compounds in a Chemical Space that share the largest possible common core with it. This is particularly useful when you do not want to restrict yourself to exact substructure matches, but still want chemistry that “stays close” to a desired scaffold, pharmacophore-bearing fragment, or privileged motif.
Beyond MCS, SpaceMACS can be applied in several complementary modes to mine a space depending on what you consider “relevant”:
- Exact Motif/Substructure Retrieval: If your objective is straightforward (“show me everything in this space that contains this ring system / warhead / linker pattern”), SpaceMACS can act as a high-throughput substructure filter. This is the most direct way to answer questions like: Which synthetically accessible analogs exist that already contain my required motif? It’s ideal for enforcing “must-have” chemistry constraints early.
- R-Group Searches: If your main question is “what decorations around a core motif of my compound do exists?”, SpaceMACS ban be used to define one or more attachment points (exit vectors). This way it will retrieve compounds that match the desired core and reports the substituents found at each attachment point. This turns ultra-large Chemical Spaces into an “on-demand SAR table”.
- Chemistry-Aware and Pattern Logic (SMARTS): If you want to very explicit about what you want or don’t want, SMARTS supports matches your needs. In SpaceMACS, SMARTS-style querying is useful when “substructure” is too vague and you need to encode rules (e.g., exact functional groups, allowed/forbidden environments, attachment-point constraints, exclusion). This enables high-control mining instead of retrieving molecules with liabilities and unwanted motifs.
Accelerate Your Project with Tangible Results
The true value of virtual discovery lies in the ability to test the results in the lab. Through our partnerships with leading vendors such as Enamine, ChemSpace, WuXi LabNetwork, Ambinter, OTAVA, and eMolecules the compounds you identify are actionable. These “make on demand” candidates are typically delivered to your table within a few weeks. You can explore the various Chemical Spaces here to begin your search.
Access the tool of the month!
We are providing full access to this technology for an entire month, giving you the opportunity to explore vast chemical landscapes at no cost.
The license will be valid until March 31, 2026 and can be used for:
Note: To utilize this license, please ensure you have downloaded either infiniSee or the standalone SpaceMACS command line version. Compatible Chemical Spaces are available here.