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Create Your Own Chemical Space

What are Chemical Spaces?

Combinatorial Chemical Spaces are ultra-large collections of molecules, typically containing billions, trillions, or even larger numbers of molecules.
Designed as the next evolutionary step beyond enumerated compound libraries, Chemical Spaces represent the largest hunting grounds for synthetically accessible molecules. They are built from two key components: chemical building blocks and predefined reactions to combine them.

If you are eager to learn more about the concept and perks of Chemical Spaces follow this link. This page is dedicated to the setup of your own Chemical Spaces.

How to Create Your Own Chemical Space

The good news is that you basically need two things to get started: Building blocks and chemical reactions to combine them.

First, the building blocks. Building blocks can come from any source, but since the aim of the Chemical Space is to provide you with tangible and accessible results, it is best to choose building blocks from a readily accessible source. Commercial libraries of building blocks are perfect for this purpose. Upon selecting your provider, keep the delivery times of building blocks in mind. "In-stock" building blocks do not have to be synthesized first and can be shipped right ahead. This sortens wait times and streamlines your workflow.

A huge augmentation to a Chemical Space comes from combining different sources because it significantly expands the chemical diversity of the potential results. Couple it with in-house, proprietary building blocks to introduce novelty and IP into the set for the best results.

Combinatorial Explosion of Compounds

The huge numbers of Chemical Spaces are the result of a combinatorial explosion that occurs when the building blocks are combined through predefined reactions. A combination of 1,000×1,000×1,000 building blocks already results in 109 compounds. Therefore, Chemical Space scale exponentially with their building blocks and included reactions.
The chemical reactions have to be written in the SMIRKS format to define the pattern how the building blocks are combined.

You can use a collection of robust, chemical reactions that was used in the creation of eMolecules eXplore Chemical Space that is available as download here as a starting point for the setup of your Space.
Again, the real value is added by adding your own in-house reactions to cover a larger area of unexplored chemical entities.

Launch Your Space with CoLibiri

The last thing that remains to create your own Chemical Space is the use of CoLibri.
The tool was developed to create ultra-large, combinatorial Chemical Spaces in a format that can be efficiently screened. Once the Space has been generated, it can be used in other BioSolveIT applications to mine for relevant chemistry based on the needs of the project.

Screening Tools for Chemical Spaces

BioSolveIT software for Chemical Space exploration:
  • infiniSee: Chemical Space navigation platform with a graphical user interface.
    infiniSee retrieves relevant chemistry from ultra-large Chemical Spaces containing billions or even trillions of compounds based on their similarity to a query compound. Results are synthetically accessible per design in one or two steps and, in the case of our partners' Chemical Spaces, can be ordered directly to your table.
  • infiniSee xREAL: Exclusive platform to screen Enamine's largest compound catalog featuring trillions of compounds.
    infiniSee xREAL contains all features of infiniSee and supports all three Chemical Space exploration search modes.
  • Chemical Space Docking™: (as SeeSAR's Space Docking Mode)
    C-S-D is a the next generation of structure-based virtual screening. In this innovative approach, ultra-vast Chemical Spaces, containing billions or even trillions of entries can be screened for the promising candidates to bind at the target structure.
Command-line tools for Chemical Space exploration:
  • FTrees: Pharmacophore-based similarity screen. Algorithm behind the Scaffold Hopper Mode.
  • SpaceLight: Retrieves close analogs based on molecular fingerprints. Algorithm behind the Analog Hunter Mode.
  • SpaceMACS: Performs maximum common substructure searches, as well as exact substructure mining. Algorithm behind the Motif Matcher Mode.

Additional Considerations

  • Pay attention to the success rate of syntheses and remove reactions that don’t perform well.
  • Adjust reactions as necessary. The impact of decorations, such as electron-withdrawing groups, can reduce the reactivity of building blocks. These can be modified using filters in the SMIRK definition.
  • Test your reaction definitions on a small but diverse set, to see if the desired product is formed and check for undesired outcomes.
  • Define your reactions and filters in a way that the product do not contain any unwanted functional groups.

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