Free Energy Perturbation (FEP): Another technique in the drug discovery toolbox
Introduction When I first started using CHARMM over 20 years ago as a PhD student, I regularly came across references ...
Spark is the next generation of our bioisostere searching tool “FieldStere”. Building on the excellent results that you have been getting with FieldStere we have introduced new science and an improved user interface with the release of Spark.
Our collaboration with Optibrium has enabled us to bring predictive ADMET models into the Spark results table. With this optional add on, every result in the table gets scored against every StarDrop model that you license or create. Once in the table you can use the predictions to filter or sort the results giving you a clear indication of the likely benefits and drawbacks of incorporating a specific bioisostere.
The Cresset proV10 range of products incorporates the next generation of our proprietary molecular mechanics XED force field. XED3 was first released with Forge and includes improved field patterns surrounding aromatic halogens, improved fields around kinase hinge binding moieties and a radical change in the handling of nitrogen. It has long been known that nitrogen atoms do not exist in exclusively planar or pyrimidal geometries yet all molecular mechanics force fields model it in one of these two states. XED3 breaks this mould allowing nitrogen atoms to flex between the two states in an analogue fashion as the degree of hybridization with neighboring groups changes.
FieldStere introduced the ability to view the results in clusters way back in version 1.1 and you’ve told us how much you value this feature. For Spark we’ve extended the clustering capability to give you multiple ways of doing the clustering making it easier than ever to find the best bioisosteres for your project. The new clustering algorithms give more control for both scaffold replacements and in experiments which grow molecules or otherwise introduce new terminal groups.
In common with Forge we’ve simplified the user interface providing clearer icons and a better interface for reading molecules. As you’ve come to expect from us we are still focused on making your experience as easy as possible so the popular wizard interface remains unchanged. The screenshot below should give you a flavor of what is new but please try it for yourself. All current FieldStere customers get a free upgrade so contact us to get your new license file and download.