Flare provides new insights for structure-based design by integrating cutting edge approaches from Cresset with significant open source and commercial methods. Use Flare to:

Flare is an intuitive GUI available on Windows®, OS X® and Linux®.

New methods for understanding your protein-ligand system

Protein interaction potentials to perfect molecule design

Flare uses the XED force field to calculate a detailed map of the electrostatic character of the protein active site. 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 interaction potentials to:

  • Reveal the electrostatics of the active site
  • Understand the requirements for ligand binding
  • Compare ligand and protein electrostatics
  • See where your ligand is sub-optimal and design improvements.

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.

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.

“Flare gives us an excellent assessment of the potential binding of hits. We use it to triage hits from a Blaze and Forge experiments in the absence of 3D-QSAR, narrowing them down to an affordable subset of the most promising hits. Flare gives us the luxury of choosing the best hits from a far larger pool than we could purchase directly.”

Robust enabling capabilities to support new workflows

Lead Finder for protein-ligand docking

Lead Finder™ predicts the 3D structure of non-covalent and covalently bound protein-ligand complexes by docking a flexible ligand to a static protein structure.

The advanced functional forms in Lead Finder provide excellent pose prediction, detailed feedback on new molecule designs and high enrichments in virtual screening. Use Lead Finder to:

  • Find novel leads through virtual screening
  • Design focused libraries by screening large virtual compound sets
  • Predict the 3D structures of active molecules
  • Dock covalent and non-covalent ligands to your protein
  • Rapidly assess new molecule designs for their fit to the protein active site.

XED force field, the foundation of success

Cresset’s proprietary XED force field is one of the most innovative molecular mechanics force fields in existence. XED uses off atom charges on electronegative atoms to give a more detailed representation of the charge density surrounding an atom, resulting in an improved description of molecular interactions.

The XED force field in Flare enables you to:

  • Minimize ligands, proteins, water and their complexes in one force field
  • Calculate detailed protein interaction potentials
  • Derive water energetics in 3D-RISM using a force field that works well for proteins and ligands.

 

 

 

The XED force field provides a detailed description of molecular electrostatics through the use of off-atom center charges. Critical to the XED molecular mechanics approach is the ability to separate partial charges into π- and σ- components.

“When dealing with systems where SAR is flat and thin, Flare could pick out and identify most of the very weak hits we have, including a novel hit that is still under examination.”

A GUI for the 21st century

Actions are always visible. Shown here with different skins (blue, white, black).

Easily compare ligand-protein complexes. In this case all available A2A crystal structures were loaded into the application and ligands automatically split out.

Each ligand in Flare can be displayed in its associated protein in grid mode making comparisons between ligands or proteins straightforward.

Protein interaction potentials reveal the electrostatics that underlie ligand binding. In this case pdb code 4G31 (red = positive, blue = negative). Widgets can be undocked at any time and placed on additional monitors.

Common picking actions on the ribbon give an extended picking widget that enables complex queries.

Brief summary and detailed log text.

Brief summary and detailed log text for RISM.