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 ...
Last month’s release of Forge GUI has received excellent feedback and now we are preparing to release the corresponding command lines binaries. We have the beta versions in testing and are expecting the release in late June or early July. The command line package will consist of three separate binaries that enable ligand alignment, 3D QSAR model building, and scoring (or fitting) to an existing model. These can be combined or used separately to perform virtual screening, automated ligand design, automated QSAR model building and automated ligand scoring against existing models.
The falign binary directly replaces the existing FieldAlign command line application and is used to align (and score) one or multiple molecules to a reference structure. As with FieldAlign, it can be used for virtual screening small sets of molecules (up to 100,000) or for automated ligand alignment as part of a design workflow. All options from the existing falign program have been retained to reduce the disruption to existing customers – just change the path to the binary and all existing scripts should work without error.
The fbuild binary takes a set of aligned structures such as those from the falign binary and creates a 3D QSAR model. All of the functions from the Forge GUI are available, along with a few more: you can choose which fields to use in the model, partition the data in various ways between training and test sets, weight molecules according to their similarity scores, and more! In addition, fbuild can export all of the raw model data, so you can apply your own statistics and QSAR techniques to our fields!
The fscore program is the counterpart to fbuild – it lets you apply a QSAR model built with Forge or fbuild to a stream of aligned molecules. As in the GUI, not only do you get an activity prediction but also a measure of how well each molecule fits within the model space.
The release of these command-line components will allow you to automate the QSAR workflow, to do small-scale virtual screening, and to make models built in Forge available to chemists through web front ends. Knime and Pipeline Pilot wrappers for these tools will be out in the near future, enabling you to integrate Forge’s unique capabilities into everything you do.
To find out more about Forge and the command-line components, contact us.