We are delighted to announce the release of a new version of Forge, our computational chemistry workbench for ligand-based design. This version, V10.3, includes over 70 new or improved features.
The development of our applications is always guided by our customers and this release is bursting with features that you have asked for. A few of these are described below but there is no substitute for using the software for yourself to see the new features in action.
- Support for multiple activities in Activity Miner – find and decipher selectivity as well as activity cliffs
- Automatic enumeration of unspecified chiral centers
- Improved conformation hunt settings that gives significantly fewer, lower energy conformations.
- New integrated FieldTemplater module – find a detailed pharmacophore from diverse ligands
- Integration with Blaze for virtual screening – submit molecules to Blaze and retrieve results straight into Forge
- New radial plots enable rapid assessment of compounds properties against project or corporate profiles
Activity Miner has been a huge hit since its release last year. You told us that you enjoy the powerful yet intuitive interface, that it has helped you to find and understand critical regions in your SAR and that it has helped your medicinal chemists rapidly assess the SAR landscape of projects. However, the number one request has been for selectivity cliffs – the use of multiple activities to look for changes that disproportionately change one activity relative to another. In this release of Forge we are have included this functionality.
Activity miner now supports multiple activities and displays activity cliff information for all activities and all compounds in a matrix of all compounds or relative to a single compound. All the new data created a major challenge – how were we going to present multiple activity cliffs using multiple similarity metrics for many compounds in an easy to understand way? However, we think we have succeeded in the task that you set us (below) but please tell us how well it works for you on your data!
Use 2 activities or even more!
There is more new science in this release beyond selectivity cliffs. In particular we’ve been looking at our treatment of molecules with an unspecified chiral center and how we perform conformation hunting. In this release we now enumerate all the possibilities in molecules loaded with unspecified chiral centers. Like selectivity cliffs, this feature has been a high priority for our users and we are delighted to introduce this new functionality.
Conformation hunting is critical to our alignment methods and hence always something that we are looking to improve, even though independent tests show that our performance is one of the best. Our research has shown that we can reduce the number and increase the quality of conformations we use with a couple of small changes to our settings. By improving the minimization of conformations, combined with taking a smaller energy window for accessible conformations, you get significantly better populations in most cases. However, these changes come with a penalty – the time taken for this type of conformation hunt is increased. As a result we’ve changed how our default ‘Accurate’ methods work to use the new settings but retained the previous settings for ‘Quick’ and ‘Normal’. The great thing is that with our standard calculation dialog box you can choose your own settings and have these quickly available for later use.
The new user interface includes custom plots, radial plots of properties, a manager for activity and the associated error data, ribbon view of proteins and auto-color of selected molecules which are requests from customers. However, one new feature that we wanted for use on our internal work, and especially our consulting projects, is a simple script interface to changing some of the values in the molecule table.
Column script editor
The column script editor provides a JavasScript interface to molecule and table data and enables modification, formatting or creation of values in the table. A simple example might be to remove the ‘>’ symbol from activity values before using them in a 3D-QSAR experiment, or coloring all values in a column called ‘HERG_IC50’ that are below 10 as red. Once developed (and we are happy to help you get your script working quickly), these scripts can be set to run on every project or exported for use by colleagues running Forge or Torch.
This release is a major advance for Forge so we encourage you to upgrade at your earliest convenience.
If you are not currently a Forge customer then now is a great time to try a free demo.
Contact us if you have queries relating to this release.