Docking in Flare uses Lead Finder™ to give you detailed feedback on your new molecule designs, high enrichments in virtual screening and excellent pose prediction.
Easily predict the binding pose and interactions of covalent inhibitors choosing your preferred covalent warhead.
Use ensemble docking with covalent and non-covalent ligands to tackle the flexibility of the protein active site by running the docking experiment on multiple protein conformations.
- Predict the 3D structure of non-covalently bound protein-ligand complexes by docking a flexible ligand to a static protein structure
- Dock covalent ligands known to bind to a particular residue in the protein, using a variety of reactive warheads
- Dock covalent and non-covalent ligands to multiple protein structures in one experiment
- Use a ligand template to seed a docking of multiple ligands that share a common substructure, ultimately leading to better docking results
- Set docking constraints to bias results to include specific protein-ligand interactions, such as H-bonds, protein metals, pi-stacking, pi-cation, or salt-bridges
- Set ‘flickering’ waters to automatically run the docking experiment with and without critical binding site waters
- Dock hundreds of compounds in parallel using Cresset Engine Broker™
- Rapidly assess new molecule designs for their fit to the protein active site
Docking multiple ligands to a single protein
Multiple analogues of the crystallographic ligand in PDB:1OIT docked into the protein’s active site. The surface of the 1OIT active site is colored by electrostatic potential (red = positive, blue = negative).
Docking covalent inhibitors
Docking of a covalent inhibitor targeting Tyrosine, displayed with Electrostatic Complementary™ surface of PDB 4QDE
Docking to multiple proteins
Docking to multiple protein structures in a single experiment with concatenated results, displayed with the electrostatic surface of PDB 5HLW. Available for non-covalent and covalent ligands.
Flickering waters
Flickering Waters is a docking method in Flare that allows explicit consideration of key water molecules in protein binding sites by permitting them to be either present or absent during docking. This enables realistic modelling of binding scenarios where conserved or transient waters may play a critical role in ligand recognition.
- Enables docking with optional binding-site waters
- Distinguishes direct ligand–protein interactions from water-mediated binding
- Clarifies the role of conserved and transient waters in ligand stability
- Supports rational decisions on water displacement vs retention during design
In Flare, Flickering Waters is implemented as part of the docking workflow. Selected water molecules in the active site are treated as optional entities that can be retained or displaced depending on the ligand pose and interaction energetics. During docking, ligands are evaluated in binding modes both with and without these waters present, with docking scores calculated for each case and reported in the project log.
The resulting poses allow users to directly compare alternative binding hypotheses, for example, whether a ligand forms stronger interactions through direct hydrogen bonds to the protein or via a stabilising water bridge, and to quantitatively assess whether inclusion of the water improves or weakens the docking energetics. These poses can be analysed interactively alongside hydrogen bonding networks, ligand efficiency metrics, and electrostatic surfaces.
- Exploring ambiguous binding modes involving bridging waters
- Assessing whether ligand modifications should replace or exploit a water molecule
- Improving interpretation of docking results in highly hydrated binding sites