A new version of Forge, our computational chemistry workbench for ligand-based design, is now released. V10.4 includes over 170 new or improved features.
The development of our applications is guided by our customers and this release is bursting with new science and features that you have asked for. A few of these are described below, however, I suggest that you use the software for yourself to discover the other features and see the new science in action.
- Activity Atlas: Summarize and decipher your SAR in 3D
- New QSAR Model Dock: save, analyze and visualize multiple (Q)SAR models in the same Forge project
- Record and recall ‘scenes’ from your project with the Storyboard
- New external REST service for properties: add your own data and properties to the Forge project
- Improved Forge Processing dialogue.
This new component enables you to summarize the SAR for a series into a visual 3D model that can be used to inform new molecule design. We believe it will particularly benefit those project teams where there is not enough SAR for a traditional 3D-QSAR approach.
Activity Atlas calculates and displays as 3D visualizations:
- The ‘Average of actives’: What do active molecules have in common?
- The ‘Regions explored’: Where have I been? For a new molecule, would making it increase our understanding? This analysis also calculates a novelty score for each molecule.
- The ‘Activity Cliff Summary’: Where are the critical regions of the SAR?
Activity Cliff Summary maps are derived from the Activity Miner module, summarizing the activity cliff data across the series into a simple map of the critical points in the SAR.
Figure 1 shows the Activity Cliff Summary for Adenosine A1, Adenosine A2a and Adenosine A3 receptor activity data for a data set of compounds published by J. Bajorath (J. Chem. Inf. Model. 51 258-266, 2011). Critical regions for SAR at the three receptors can be easily visualized and used to inform new molecule design aimed, e.g., at maintaining potency at the A1 receptors while building in selectivity towards A2 and A3.
Figure 1: Activity Cliff Summary for Adenosine A1 (left); Adenosine A2a (middle); and Adenosine A3 (right).
Color coding of maps: Red: more positive increases activity; Blue: more negative increases activity; Green: steric bulk in this position is favorable; Magenta: steric bulk in this position is detrimental.
QSAR Model Dock
The introduction of Activity Atlas models has led to model handling in Forge being radically overhauled so you can save, analyze and visualize multiple (Q)SAR models in the same Forge project.
Forge now has a simple drop down box for choosing which model you wish to use or display (Figure 2). This makes it easy to compare models built against different targets or using different methods (3D-QSAR, Activity Atlas or k-Nearest Neighbours). You can now build a number of models for one or more targets and use only those with the best performance, or quickly switch between models against different activities.
Figure 2: QSAR Model Dock drop down box in Forge
Record and recall ‘scenes’ from your project with the Storyboard
The Storyboard (Figure 3), new in V10.4, records ‘scenes’ from the 3D window that can be recalled with a click. All details of the 3D window will be recorded, for example:
- The presence or absence of measurements
- Any existing surfaces or models
- The view center
- Selected molecules, etc.
The Storyboard enables you to communicate project data with colleagues through recording of a story consisting of several scenes and as a way of recording important results in your project. The Storyboard is also a very practical way of moving across different (Q)SAR models built using different methods against different activities, with only the click of a mouse.
Figure 3: Storyboard
New external REST service for properties
One of the most requested features by customers is the ability to include corporate or externally-computed data for any compound into the Molecules Table. This is now possible as Forge V10.4 can connect to an external web service, through a REST interface, to import external properties and data computed or retrieved by such web services as additional columns in the Molecules Table. Using the new service you can bring in external predictions for new designs or simply use the corporate algorithm for calculating logP. Once imported the properties can be used in the Radial Plot, Tiles View and for coloring molecules and table cells enabling you to study how the 3D shape and a custom property of molecules varies.
Try the New Forge
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 download a free evaluation.
Contact us if you have queries relating to this release.