Spark CSD Fragment Database
Cresset’s Spark CSD Fragment Database can be used within Spark as an exciting and powerful way of generating novel and diverse structures for your project.
Spark is a bioisostere replacement tool. It uses the electrostatic and steric properties of molecules to rank new scaffolds and R-groups in the chemical context in which they will be synthesised. Using Cresset’s field technology, based on the XED force field, Spark is a highly efficient and rich source of new directions for a project.
A major advantage of Spark is that it scores each potential replacement in context. Each candidate replacement fragment is merged into the starting molecule before scoring using electrostatics and shape. While most Spark databases use calculated conformations for the shapes of the fragments, the Spark CSD fragment database uses the experimentally-determined and expert-curated fragments and conformations from the CSD as a source of novelty giving you confidence in the conformation of the new fragment.
Using the Spark CSD Fragment Database in Spark you can:
- perform scaffold hopping on known active compounds
- explore new R-groups and scaffolds from the CSD
- use experimentally proven fragment conformations in your molecules.
Example: Finding bioisosteres of Sumatriptan
Cresset’s Spark was used to search the Spark CSD Fragment Database to identify potential R-group replacements of the sulphonamide group of Sumatriptan (circled in red).
Both aromatic and aliphatic alternative R-groups were identified by Spark among the top-ranking results. These compounds are similar to Sumatriptan in terms of whole molecule electrostatic and steric properties and are accordingly potential bioisosteres of this starting structure.
The most interesting results are shown below, together with the relevant field points and the negative electrostatic field surrounding the compounds. These were calculated using Cresset’s field technology.