Protein and ligand electrostatics to perfect molecule design
Flare uses the XED force field to calculate a detailed map of the electrostatic character of the protein active site and your ligand. The interaction potentials provide you with vital knowledge of the fundamental processes that underlie ligand-protein binding, helping you to perfect the design of new molecules. Use protein and ligand electrostatics to:
Reveal the electrostatics of the active site
Compare electrostatic patterns across a protein family to design more selective ligands
Design new molecules with the ideal electrostatic properties to bind strongly to your protein
Gain vital insights into your SAR by comparing the electrostatics of multiple ligands.
Electrostatic complementarity map for PDB entry 4UIV illustrating areas where protein-ligand electrostatics are favorable (green) and where electrostatics could be improved (red).
Full protein interaction potential maps guide the placement of ligand atoms.
Interaction fields can be mapped onto protein surfaces allowing quick and easy visual assessment of electrostatic trends across protein families.
Designing new ligands in Flare gives you immediate feedback on electrostatic changes while viewing your molecule in the protein active site.
Electrostatic interaction potentials can reveal electrostatic trends in chemically divergent molecules.
Electrostatic complementarity surfaces can be generated for ligands, displaying areas where protein-ligand electrostatics are favorable (green) and areas where the ligand could be modified to improve protein-ligand binding (red).
Fast and interactive activity prediction
Predict activity by comparing the protein interaction potential with the electrostatic character of the ligand. Gain immediate feedback on where to optimize the ligand-protein interactions through a visual representation of the Electrostatic ComplementarityTM. With Electrostatic Complementarity you will:
Predict the activity for every new design in seconds
Gain immediate feedback on where your ligand complements your protein and use this in design
See where your ligand is sub-optimal and design improvements.
Cresset’s innovative Electrostatic Complementarity TM scoring provides rapid feedback on new molecule designs. Green: Prefers ligand. Red: Prefers water.
Quick, easy and accurate docking
Predict the 3D structure of non-covalent bound protein-ligand complexes by docking a flexible ligand to a static protein structure. Tackle the flexibility of the protein active site with ensemble docking run on multiple protein conformations. This elegant workflow is easy to set-up, fast to run and gathers the results into a single set of poses that are easy to navigate. Docking in Flare uses Lead Finder™ to provide excellent pose prediction and detailed feedback on new molecule designs. Use it to:
Rapidly assess new molecule designs for their fit to the protein active site.
Multiple analogs docked to a single protein displayed with a hydrophobicity surface.
Docking to multiple protein structures in a single experiment with concatenated results, displayed with the electrostatic surface of PDB 5HLW.
WaterSwap for ligand energetics
WaterSwap is a thermodynamic integration method for investigating ligand-protein energetics. It enables you to:
Investigate energetics of ligand binding
Decompose binding energies into per-residue components to find optimal interactions for your ligand
Calculate ΔG of binding for a series of ligands to help prioritize your designs.
Green residues show where the ligand is gaining the most energy from interaction. Red residues show where water binding is preferred and represents opportunities to improve ligand design.
3D-RISM for water stability and positioning
The position and energetics of water molecules in and around the active site is of crucial importance in understanding ligand binding. Knowledge of which water molecules are tightly bound and which are energetically unfavorable can give valuable insights into structure-activity relationships and help you to decide where to place ligand atoms. Cresset’s 3D-RISM analysis utilizes the advanced inter-molecular descriptions of the XED force field to give you a water analysis you can trust. Use 3D-RISM to:
Understand water energetics of your protein
Calculate optimal locations of water around your ligands
Design new ligands and understand their water interaction in a few minutes on your laptop
Perfect protein interaction potentials by including stable waters in the analysis.
Customize and automate your tasks using Python
Create your own workflows, automate your common tasks, expand Flare with Python modules and add custom menus using the Python API. The Python API gives full access to all of Flare’s capabilities, including the RDKitTM cheminformatics toolkit. Use it to automate common tasks and customize the interface for your needs. Upgrade Flare with Python modules for graphing, statistics, Jupyter® notebook integration and much more. Command line Python scripts allow simple automation and distribution of Flare calculations.
The Python console allows Python commands to be entered into Flare and displays their output inline as either text or images. This screenshot shows an example script which loads a series of SMILES strings through the RDKit SmilesParser, generates 3D conformations using the XED force field, docks them using Lead Finder and displays a scatter plot of the RDKit-computed Crippen logP against the binding ΔG computed by Lead Finder. The Flare Python API can be usefully combined with other Python modules to generate and analyze results.
Actions are always visible.
Compare ligand-protein complexes
Easily compare ligand-protein complexes. In this case all available A2A crystal structures were loaded into the application and ligands automatically split out.
Focus on ligands
Flare has a dedicated table for your ligands. It calculates key physicochemical properties and enables you to combine them into a single multiparametric score. Ligands can be tagged, sorted and organized into custom groups. Use the Python API to add your own properties to the table, or create insightful graphs and plots.
Each ligand in Flare can be displayed in its associated protein in grid mode making comparisons between ligands or proteins straightforward.
Tell your story
The storyboard enables you to capture and communicate your insights into your ligands and proteins. Every snapshot can be custom titled, annotated with key points, and recalled into the main window.
Common picking actions on the ribbon give an extended picking widget that enables complex queries.