Toolkit for the analysis of virtual combinatorial library and patent Markush structures
Markush structures, or generic structures, are widely used in combinatorial libraries and chemical patents to define large chemical spaces. ChemAxon provides the most advanced Markush technology, including rapid structure search in Markush space, enumeration, overlap analyses, and automatic Markush composition. All Markush analysis features are available as an add-on for ChemAxon’s JChem technology (JChem Base, JChem Cartridge and Instant JChem).
ChemAxon’s solution for handling Markush structures
ChemAxon’s market-leader Markush representation supports all important structure variations to be able to handle combinatorial virtual libraries and complex Patent Markush structures, such as atom lists, bond lists, position variation bonds, link nodes and repetition units. Advanced Markush features, such as multiply-connected R-groups, heavily nested R-groups, R-group bridges and homology groups are also supported. ChemAxon’s .mrv file format fully supports all current Markush features.
Marvin and Marvin JS as general drawing tools are perfect for handling smaller Markush structures but not for structures with hundreds of fragments. Markush Editor is designed for creation and visualization of complex combinatorial and patent Markush structures. With built in Composer wizard you can generate Markush structures automatically and by validation, enumeration, hit and non-hit visualization you can analyze them easily.
Besides drawing it manually, a Markush structure can also be generated automatically using R-group decomposition or Markush Composer. R-group decomposition identifies all R-group substituents, starting with a structure library and the definition of the common scaffold. Using these substituents an R-table or a Markush structure can be created. Markush Composer can calculate the optimal scaffold automatically and it can generate combinatorial, and also complex patent Markush structures. The created Markush structure, covering all possible combinations of your starting compounds, can be ideal starting point to generate new ideas or create your own patent Markush structure.
Markush Enumeration is a powerful tool for Markush structure analysis and is fully implemented in JChem. By interactively guiding the enumeration of the Markush Structure users can quickly understand the relevance of Markush to their needs. Current enumeration types include; full, partial, and random enumeration; library size calculation; homology enumeration.
Markush Overlap analysis
Markush Overlap analysis is a powerful automatic analysis technology to compare two Markush structures. Capable to calculate the overlapping chemical space between two Markush compounds regardless of the complexity of the molecules. The percentage of overlap and the Markush representation of the overlapping chemical space can be calculated.
Markush Non-hit visualization
Markush non-hit visualization is a powerful visual analysis technology to compare a Markush structure and a compound. Capable to highlight both the matching and non-matching parts in a query structure and in the R-groups of a target Markush structure. The differentiating parts can be easily recognized and analyzed this way.
ChemAxon’s Markush Search
Searching in Markush spaces
Markush Search is a powerful tool for structure search in a large chemical space defined by a generic Markush structure, without actually enumerating the explicit compounds. This approach enables the exploration of extremely large Markush spaces, which would be unthinkable by traditional search techniques. In case of multiple substructure queries against a library of Markush structures, an “Overlap Analysis” can be applied, returning the hits for each query structure separately. ChemAxon’s Markush technology now allows users to submit Markush structures of limited complexity as a query. Query Markush structures can contain the same Markush features that can be present in general Markush structures, which makes the comparison of simple Markush spaces possible.
Rich visualization features
Hit coloring and automatic structure alignment make the visualization of the search results easier. The features for better visualization include 2D-cleaning for the hit structures. Users may also choose to reduce visualization on the Markush core only. Alternatively, non-relevant R-groups can be filtered out to display only essential information or all R-groups can be shown. For an even “cleaner” display, Markush Reduction can be applied.
Markush structures in a workflow
Workflow management solutions play a more and more important role in everyday research processes. ChemAxon’s Markush analysis plug-in is implemented in KNIME and in Pipeline Pilot, two commonly used workflow management tool-kits. These implementations includes Markush Search, Markush Enumeration, and Markush structure generation which makes this technology easily accessible and integratable into best practice routines.