Free advice for SMEs on how computational chemistry can advance your project
Through our partnership with the Medicines Discovery Catapult we are offering a limited number of computational chemistry consultancy sessions to ...
The release of Flare V2 brings quicker analysis of new design ideas and more automation of workflow processes. Andy Smith explains the advantages that Flare V2 brings to Cresset Discovery Services customers, including more time spent on high-value design and analysis work.
Before a new version of the software is released, we have already applied the new functionality to our customers’ projects once it has been fully validated by our development team. This means that in additional to the existing available packages within our software Cresset Discovery Services customers get to the added benefit of the upcoming functionality before it is generally released. We always send files which are compatible with customer’s software: if pre-release functionality is used to illuminate our analysis, we save the data in a format so that customers can still review the analysis. Flare V2 opens up exciting new functionality to Cresset’s software customers that invariably has already been extensively tried out by the Cresset Discovery Services team.
The Flare development which has us most excited and is likely to benefit our customers the most is the ability to calculate the Electrostatic Complementarity (EC) of protein-ligand complexes, and project the values onto surfaces for both the proteins and ligands.
EC is a new method developed inhouse by Cresset scientists that distils complex protein ligand interactions into an obvious and informative pair of surfaces which are accessible and understandable to a broad-spectrum audience.
I recently showed the EC feature in Flare V2 to a group of senior medicinal chemists. They were very impressed with the intuitive representation. They commented that the visual surfaces were consistent with their understanding of the SAR of the system, and also added, ‘This will make a great series of pictures for the CEO to use.’ I took this as a huge endorsement of the EC calculations and visualization!
Figure 1: Electrostatic Complementarity surfaces for the Aurora A kinase 6hjk crystal structure.
The data available from an EC calculation feels similar to that obtained from a Fragment Molecular Orbital (FMO) approach but at a small fraction of the computational expense and in a more visually intuitive form. Within Flare it is possible to process hundreds or thousands of ligands in a reasonable time frame, allowing for live EC analysis of ideas during meetings.
We worked with a team in a brain storming session and used the EC surfaces to quickly highlight the good and bad ideas and emphasize regions of the ligand that required additional attention.
At Cresset Discovery Services we are now using EC as an additional scoring and filtration method for docking and virtual screening ranking, and to further evaluate protein ligand interactions.
Python has become an increasingly popular and useful scripting language amongst the chemistry and cheminformatics communities, particularly when combined with the RDKit. Flare V2 features a Python API that provides access to all functionality available within the Flare graphical user interface from a Python script. Furthermore, the Flare V2 Python environment allows tight integration with the RDKit: native Cresset methods and RDKit methods can be used interchangeably on molecules loaded into a Flare project. The Python API and the RDKit integration also have an important automation focus feature rather than a purely scientific advancement, and the ability to use Python and the RDKit from within Flare allows fully customizable workflows to be designed and executed.
Including Python and the RDKit directly into Flare makes the process of using Python and the RDKit far smoother. Coupled with the support expertise available from Cresset and the vibrant Python RDKit community it makes this an exciting addition.
I’ve been using the Python RDKit integrated tools and workflow to automate standard protocols, which frees more of my time for the interesting design and analysis work for which Cresset Discovery Services are known. Processing and managing molecules in Flare V2 just got a whole lot more efficient, which means we can pass on this time saving to customers as extra time for analysis or design.
If you’d like to discuss how Cresset Discovery Services can deploy these new tools to advance your project, please contact us for a free confidential discussion.