Explore alternative R-Groups to escape ADMET traps
Powered by Cresset’s field technology, Spark’s ‘product-centric’ approach to bioisosteric replacement enables users to rapidly generate diverse, non-obvious bioisostere ideas in a variety of different experiments.
In an R-Group replacement experiment, Spark will explore replacements of functional groups that are important for binding, but problematic in terms of ADMET properties. In this way, Spark will help you accelerate lead optimization and reduce the risk of late-stage attrition.
Wizards make running Spark experiments simple by guiding you step-by-step through experiment set-up and execution. In an R-Group replacement experiment, you select the R-Group in your molecule to replace, and in just a few clicks, Spark generates a list of new possible alternatives with similar electrostatic and shape properties, but different chemical structures.
The R-Groups will be taken from your choice of Cresset-generated fragment databases available to all Spark users. Fragments are derived from real molecules from a variety of sources: commercially available compounds and reagents, literature reported compounds, patent data, degrader linkers, agrochemical compounds, small molecule crystal structures, and theoretical ring systems. You can also create your own reagent and fragment databases if you wish, using Spark’s database generator.
After the experiment completes, Spark integration within Flare gives access to a wide range of methods for result refinement and post-processing, including Electrostatic Complementarity™, docking, MM/GBSA, Flare FEP.