Flare enhances the Cresset Discovery Services toolbox

One of the advantages of working for Cresset Discovery Service is that I have access to software that is under development. I’ve therefore been working successfully with Flare, our newly-released structure-based modeling application, on client discovery projects for some time and I’m delighted that it is now available to a wider market.

Processing structures to extract discovery information

So, what does Flare offer Cresset Discovery Services that it didn’t have before? Forge is the comprehensive workbench for ligand-centric workflows and I use it as the main workhouse for ligand work. However, more and more drug discovery projects are now structure enabled.

In fact, the increasingly routine use of X-rays and Cryo-EM means that projects generally have access to lots of structures, not just one. Processing these in order to extract useful information is often a key step for us on client projects. For this structure enabled work, Flare has become my Forge equivalent – my main workbench for structure-based work.

Using Flare

The Flare GUI is intuitive and easy to navigate, yet already has significant, powerful and unique functionality. From a practical point of view, Flare is stable on loading 20 or more X-ray structures, and doesn’t slow down (unlike some other tools) or glitch. These structures can be automatically aligned by sequence (Cobalt) and superimposed at the click of button.

Protein preparation is automated. Water analysis via 3D-RISM allows exploration of key water molecules around ligands and binding pockets. Of course, Cresset’s own electrostatic fields can now be visualized on selected protein surfaces, in addition to ligands.

Lead Finder is a Flare plug-in that gives the capability to dock ligands and ultimately conduct high throughput structure-based virtual screening as a complementary addition to Cresset’s state of the art ligand centric-virtual screening service using Blaze.

Zika virus protease PDB : 5H6V and a covalent inhibitor. Protein positive fields (left), negative fields (middle) and ligand fields (right).

Flare is focused on ligand design

The addition of Flare to the Cresset Discovery Services toolbox enhances our client offering with a new degree of confidence for structure-based work. Flare has been developed based on input from scientists in industry and academia so that it is relevant to real discovery workflows. My own work on client projects also contributed to the design of Flare, and I know from personal experience that it is ideally suited to the needs of computational chemists.

The upshot of this is that Flare has been created with ligand design as a central task. This means that even the most computationally intensive tasks are tailored to the effect that they have on the molecules that you make. This really is the great power of computational chemistry; informing and enhancing the discovery of the molecules that matter to your project, using the best computational methods at our disposal. Flare greatly eases that task and is a great addition to our toolbox.

A single force field across ligands and proteins

However, what really puts Flare apart from other structure-based methods is the seamless use of the XED forcefield between ligands and proteins. This means that I can make calculations on structure-ligand interactions based on a continuous force field, and make meaningful comparisons at all stages of work.

Ever since I joined Cresset in 2012, customers have been asking me, ‘Why not apply the XED force field to proteins?’ I’m delighted that this question has finally been answered with the release of Flare.

Contact us for a free confidential discussion about how cutting edge ligand and structure-based methods can transform your discovery.

Launch of Flare

Flare™ 1.0 is released and available for evaluation! Flare is designed to bring you new insights for structure-based design in a modern, easy to use interface that provides a framework for future growth. Flare combines the best of Cresset research with cutting edge methods from academia and selected commercial partners to give you a deeper understanding of protein-ligand complexes that will inform and improve new molecule design.

The Flare GUI includes ligand and protein windows that enable you to create and browse through the structures that are important to you.

New methods for understanding your protein-ligand system

Key new technology available in Flare 1.0:

  • Visualize the electrostatics of the protein active site using protein interaction potentials
  • Calculate the positions and stability of water in apo and liganded proteins using 3D-RISM
  • Understand the energetics of ligand binding using the WaterSwap technique.

Protein active site electrostatics, visualized through protein interaction potentials clearly indicate areas of favorable ligand binding such as the electron rich pyrrolo-pyrimidine hinge binding motif in this PERK kinase inhibitor (PDB 4G31).

Robust enabling capabilities

Robust enabling capabilities support the new technology in Flare, providing you with:

  • Protein preparation
  • Ligand docking
  • Minimization using the XED force field.

Docking experiments in Flare are easily configured using one of the preset settings or can be customized with advanced options.

Intuitive  GUI

Flare has a logical menu structure using the ‘tabbed’ menu system to provide functionality that is easy to find and use. We’ve extended the approach to experiment setup that we have developed in our ligand-based tools to enable you to rapidly start a new experiment with a set of reliable default parameters or customize and save your own for future use.

The tabbed menu structure enables rapid identification of the functionality that you desire. For example the View tab contains functions related to the 3D view of the molecules such as the options to enable full screen mode or stereo mode

Try Flare for new insights

Flare is a new generation of structure-based design applications designed to give you new insights into your small molecule discovery project.

Evaluate Flare today.