Spark™
Ligand growing and docking
Pick additional interactions from the active site of your protein with Spark ligand growing experiments
Selecting the region of your ligand to grow from.
Spark wizard-based interface to guide you through the setting of the Spark ligand growing experiment.
Importing the starter ligand (top) to be grown with Spark using the reference ligand (bottom).
Choosing the fragment databases to run the ligand growing fragment search from.
Starter and reference ligands (top left) and results (ranked using Cresset’s unique molecular field technology) from the ligand growing experiment, displayed in Spark.
Grow ligands into new spaces, guided by an existing ligand or fragment
With Spark’s ‘Ligand Growing’ experiment you can grow your starter molecule to pick additional interactions with the active site of your protein and increase its binding affinity, guided by existing ligands or fragments mapping a different region of the same active site.
- Load the starter molecule into Spark, in its bioactive conformation
- Load additional ligand(s) to guide the growth of your starter molecule
- Select which fragment collections will be searched from a wide range of available databases
- Optionally customize your Spark search by applying physico-chemical and structural filters during the search
Selecting the region of your ligand to grow from.
Spark wizard-based interface to guide you through the setting of the Spark ligand growing experiment.
Importing the starter ligand (top) to be grown with Spark using the reference ligand (bottom).
Choosing the fragment databases to run the ligand growing fragment search from.
Starter and reference ligands (top left) and results (ranked using Cresset’s unique molecular field technology) from the ligand growing experiment, displayed in Spark.
Selecting the region of the starter molecule to replace during the Spark docking experiment.
Spark wizard-based interface to guide you through the Spark core or R-group replacement experiment with docking scoring applied.
Selecting ‘Docking’ as calculation method and specifying the scoring settings for the Spark docking experiment.
Selecting which fragment databases should be searched as part of the Spark docking experiment.
Reference ligand (top left) and results from the Spark docking experiment, showing each molecule’s binding pose, and the hydrogen-bond ligand-protein interactions. Results are ranked by Lead Finder’s ‘Docking’ score, optimized to reproduce the correct crystallographic pose of ligands.
Grow your ligands into unexplored parts of your protein's active site
In cases where no ligand is available to guide the growth process, Spark ‘Docking’ experiments enable you to grow your ligands into unoccupied parts of the protein active site, picking new ligand-protein interactions directly from the active site.
The 'Docking' method in Spark uses the Lead Finder™ algorithm to calculate a docking score for each binding pose and prioritize the best result molecules.
- Select a region of the starter molecule to replace or to grow from, and remove these atoms
- Load a prepared version of the protein to be used in the Spark docking experiment
- Find new suitable fragments to place in a sensible orientation within the active site of the protein, guided by Cresset’s unique XED force field model of electrostatics
Selecting the region of the starter molecule to replace during the Spark docking experiment.
Spark wizard-based interface to guide you through the Spark core or R-group replacement experiment with docking scoring applied.
Selecting ‘Docking’ as calculation method and specifying the scoring settings for the Spark docking experiment.
Selecting which fragment databases should be searched as part of the Spark docking experiment.
Reference ligand (top left) and results from the Spark docking experiment, showing each molecule’s binding pose, and the hydrogen-bond ligand-protein interactions. Results are ranked by Lead Finder’s ‘Docking’ score, optimized to reproduce the correct crystallographic pose of ligands.