Flare™ FEP: Competitively combining speed and accuracy with ease of use
Free Energy Perturbation (FEP) calculations arm the drug hunter with highly accurate binding affinity predictions for ligands. This accuracy can ...
We are delighted to announce the release of Blaze V10.2. This version of our unique virtual screening software contains major enhancements to the workflow that improves results and reduces the search time, a new REST interface to enable enhanced integration and an improved security system. We have also released a new fully functional Blaze Cloud demo server.
We’ve taken a fresh look at the workflow of a typical Blaze experiment. We use a search cascade (right) in Blaze to enable us to process large databases of compounds (typically up to 10 million) in a time efficient but detailed manner. The cascade uses field finger prints (FieldPrints) to do a rapid search across the entire database. However, we know that methods derived from distilling the field down to a simple vector representation are not as accurate as performing full alignments and therefore developed a quick alignment method ‘FieldClique’ to do exactly this. In FieldClique we perform a rapid alignment and single point score to get a good estimate of the final optimized alignment score. This method is significantly more accurate than FieldPrint but still less accurate than the fully optimized alignment score which we get from a FieldSimplex routine. The accuracy of these 3 different methods is used to cascade the number of compounds through the virtual screening experiment. All compounds receive a FieldPrint score, around 30-50% receive a FieldClique score and around 5% receive the most accurate FieldSimplex score.
We have been looking at improving the performance of the screening cascade for some time with a desire to fully align more molecules. For customers with GPU clusters this is less of a problem as the throughput of the GPU code is so good. In this release of Blaze we have introduced a new algorithm for the FieldClique method that enables a much greater throughput of molecules but at the cost of some accuracy. The new algorithm is around four times faster than the previous one, enabling 4 times as many molecules to be processed in the same time. In testing we have found that the loss of accuracy is more than compensated for by the ability to process more molecules in a full 3D alignment method and by subsequent FieldSimplex refinements. We recommend that whenever computing resources are available you should be refining greater than 50% of the FieldPrint results using the new fast FieldClique routine.
|Number of compounds||FieldPrint||FieldClique||FieldSimplex||Typical Time using 250 CPU cluster|
|Normal Mode||4 500 000||1 500 000||150 000||4 hours|
|Fast Mode||4 500 000||3 000 000||150 000||2.3 hours|
This version of Blaze comes with a new RESTful web service that enables you to interact with Blaze through many different environments. The fully documented methods provide access to all of Blaze’s features including searching, collection management and result retrieval. This highly requested feature provides easy integration with workflow solutions such as KNIME and Pipeline Pilot and enables Blaze integration with custom software solutions as well as enhancing the integration with future versions of Cresset’s desktop applications such as Forge.
A KNIME workflow for searching Blaze