Forge V10.4 released

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.

Highlights

  • 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.

Activity Atlas

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.

Activity Cliff Summary for Adenosine 1 (left); Adenosine 2 (middle); and Adenosine 3 (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.
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.

QSAR_Model_Dock_v10.4

Figure 2: QSAR Model Dock drop down box in Forge

Additionally, all the model building information windows have been rolled together into a single widget to significantly enhance the information flow when working with models and reduce GUI clutter while performing other tasks.

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.

Storyboard_v10.4
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.

Keeping the right chemistry in compound procurement

What happens when virtual screening libraries meet the real world?

Virtual screening libraries can be brilliantly designed to deliver the best range of chemistry for your wet screen, but when the virtual meets the real, things get more complicated. Including computational chemistry in the procurement process means that you can move from virtual screening to plated compounds and still keep the best of both worlds.

Read the full article in Outsourced Pharma.

Martin
Dr Martin Slater
Director of Consulting Services

Monash University Faculty of Pharmacy and Pharmaceutical Sciences, Australia, licenses Cresset’s computational tools

Cambridge, UK – 25th November 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that Monash University Faculty of Pharmacy and Pharmaceutical Sciences, Australia’s leading pharmacy and pharmaceutical science educators and researchers, has licensed Cresset’s Forge and Spark software. These applications provide extensive capabilities in SAR analysis, ligand-based molecular design and bioisosteric replacement.

“Cresset’s software is used in the R&D departments of the world’s leading pharmaceutical companies. It is great to know that our students will be using the very same cutting edge tools for their molecular design and optimization work,” says Dr David Manallack, Senior Lecturer at Monash University. “Cresset’s software will enhance our teaching methods, helping us to prepare our students for frontline roles in drug discovery and development.”

“Cresset strongly supports academic research. We are delighted that Australia’s Monash University will be using Forge and Spark in their teaching programs,” says Dr David Bardsley, Cresset’s Commercial Director. “These world class tools will ensure an excellent grounding in modern drug discovery techniques for the next generation of Australia’s scientists.”

Monash_Cresset_edited-1

Proximagen licenses Cresset’s computational tools for scaffold identification and bioisostere replacement

Cambridge, UK – 18th November 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that Proximagen, a company focused on the development and commercialization of novel therapeutics for diseases of the central nervous system (CNS), has licensed Cresset’s Forge and Spark software. These applications provide extensive capabilities in SAR analysis, ligand-based molecular design and bioisosteric replacement.

“Proximagen has successfully used Cresset’s computational chemistry tools in the past to generate pharmacophores from known ligands and to identify novel chemical series by scaffold hopping,” says Dr Ed Savory, Deputy Head of Chemistry at Proximagen. “We will be using Spark to identify new drug scaffolds and to make bioisosteric core replacements. Both Spark and Forge are now important and valuable components of our drug discovery program.”

“We are delighted that Proximagen have chosen to further the collaboration with Cresset,” says Dr David Bardsley, Cresset’s Commercial Director. “Cresset’s continual striving for outstanding science delivered in usable software is translating into valuable results for our customers.”

Proximagen_Cresset

Unprecedented control over scaffold hopping searches with Spark V10.3

New fragment databases give 25% increase in available chemical space

Cambridge, UK – 30th October 2014 – Cresset, provider of computational chemistry software and services, announces the release of Spark V10.3 for scaffold hopping and R-group exploration. Spark finds biologically equivalent replacements for sections of an active molecule, generating new ideas and helping you escape patent or toxicity traps. New in this release:

  • Significantly improved viewing, analysis and sharing capabilities help identify compounds with the best balance between novelty, synthesizability and physical properties
  • 25% increase in the number of fragments, giving a greater opportunity to find new IP
  • New advanced filters ensure the drug-likeness of results and narrow the search to specific changes that interest you.

“Spark experiments return structures you have thought of yourself, plus new structures that make chemical sense and are totally unexpected,” says Dr Tim Cheeseright, Director of Products at Cresset. “This new release makes it significantly easier to evaluate and share your results. The new tile view lets you select and view the structures and properties that matter most to your project. Individual chemists can flag key results, add notes and share projects with team members.”

“Spark V10.3 gives users unprecedented control over scaffold and fragment searches,” adds Dr Mark Mackey, Chief Scientific Officer at Cresset. “You can focus your search by filtering on SMARTS patterns or physical properties, so that the results all have the physicochemical profile required by your project.

“In addition, we have enlarged the number of reagents for use in lead optimization and hit growing from 150,000 to over 590,000. This provides a rapid assessment of the synthetically available choices around a lead compound, increasing novelty and reducing the design time for new molecules.”

spark10.3_release
Spark’s significantly improved results analysis helps you identify the best bioisostere for your project

Web clip: Spark V10.3 – Using Spark’s tile view and tags to rapidly assess scaffold hopping results

Version V10.3 of Spark, Cresset’s computational chemistry software for idea and bioisostere generation, includes the ability to ‘tag’ results with a custom user-defined note that can be used for sorting, filtering, and decision-making. This expands on the ‘favorites’ designation in that tags can be used to explain why a result was flagged as a favorite. For example, you can tag suggested results as being known already, interesting, synthetically unfeasible, or any other designation that you might need.

The tile view of results allows for rapid assessment of the bioisosteric substitution, along with selected properties in a tiled view. This allows for a stream-lining of the visualization of many results from the Spark experiment and can be sorted and filtered the same way as the regular spreadsheet view in the Molecule Table.

See this in action in the web clip below and contact us to find out more.

Nagoya University’s ITbM, Japan, licenses Cresset’s computational chemistry software to accelerate their research

Cambridge, UK – 28th October 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that Nagoya University’s Institute of Transformative Bio-Molecules (ITbM), creator of cutting edge science, located in Nagoya, Japan, has licensed Cresset’s Forge, the powerful computational chemistry suite for understanding SAR and molecular design.

“The focal point of ITbM is to develop transformative bio-molecules that will be key to solving urgent problems at the interface of chemistry and biology,” says Associate Prof. Ayato Sato, Head of Research Promotion Division and the chief coordinator of ITbM Chemical Library Center, ITbM Nagoya University, Japan. “We are confident that licensing Cresset’s software will accelerate our research to find candidates of transformative bio-molecules.”

“Working with Cresset’s tools has helped me generate new ideas for my projects in various disease areas,” adds Dr. Anupriya Kumar, WPI Postdoc Fellow, ITbM Nagoya University. ”The molecular visualization has made it easier to communicate my ideas to my experimental collaborators, both chemists and biologists.”

“We are delighted that Cresset software is assisting Japanese biomolecular research,” says Dr David Bardsley, Commercial Director at Cresset. “Forge uses the shape and electrostatic character of molecules to create qualitative and quantitative 3D models of activity. It is the ideal tool to assist ITbM in their research.”

ITbM_Cresset

Selvita licenses Cresset’s computational tools for SAR analysis and ligand-based design

Cambridge, UK – 2nd September 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that Selvita S.A., a drug discovery company located in Krakow, Poland, has licensed Cresset’s Forge and Spark. These applications provide extensive capabilities in SAR analysis, ligand-based molecular design and bioisosteric replacement.

Dr. Mariusz Milik, Head of Computational Chemistry at Selvita says “We are currently focused on target based design, however, as requirements of our projects change, we need to include ligand based approaches in the methods we use. We anticipate using Cresset’s software as a key component in our discovery chemistry capabilities”

“At Cresset we are delighted to see growth in the emerging drug discovery market of Central and Eastern Europe,” says Dr David Bardsley, Cresset’s Commercial Director. “Both Forge and Spark will enhance Selvita’s chemistry capabilities. The Spark reagent databases will enable them to inform synthetic decisions, whilst Forge will give control and insight into their activity data enabling them to plan the direction of their projects with confidence.”

Selvita_Cresset

CloudScientific appointed as Cresset’s distributor in China

Cambridge, UK – 9th July 2014 – Cresset, innovative provider of computational chemistry software and services, announces the appointment of CloudScientific as distributor of their computational chemistry software in China.

“The appointment of CloudScientific provides us with a dedicated channel to deliver our tools to the Chinese marketplace and will enable us to respond to the specific needs of potential customers in China” said David Bardsley, Commercial Director at Cresset. “CloudScientific has an established record of collaboration with its customers. I look forward to working with them to increase our presence in this important market.”

“We are delighted to represent Cresset who have an excellent scientific reputation and bring a portfolio of leading computational chemistry products,” said Andrea Li, Marketing Manager at CloudScientific. “We look forward to introducing these tools to the Chinese market and helping drive growth and enhanced commercial success in the future.”

CS_Cresset_edited-1

Forge V10.3: Significant new science, visualization and integration for leading ligand-based drug design workbench

Cambridge, UK – 3rd July 2014 – Cresset, innovative provider of computational chemistry software and services, announces the release of Forge V10.3. This major new release includes significant enhancements to the science, visualization, and integration of Forge, the computational workbench for ligand-based drug design, including significant enhancements to Activity Miner.

“Activity Miner has been a huge hit since its release as part of Forge last year,” says Dr Tim Cheeseright, Director of Products at Cresset. “Customers have found it invaluable for finding and understanding critical activity cliffs in the SAR landscape. In response to customer requests we have now added selectivity cliffs – the use of multiple activity parameters to look for changes that disproportionately change one activity relative to another.”

“Even though independent tests show that our performance is one of the best, we have still made improvements,” says Dr Mark Mackey, CSO at Cresset. “Forge V10.3 includes improved conformation hunt settings that give significantly fewer, lower energy conformations, enabling you to find the correct alignments even more reliably.”

Major highlights of Forge V10.3 include:

  • Find and understand structure-selectivity relationships in Activity Miner
  • Perfect the design and activity profile of new molecules using 3D-QSAR models for both primary and secondary activities
  • Rapidly analyse large datasets by connecting Forge to cloud or local cluster resources to perform calculations using the Cresset Engine Broker module
  • Create detailed pharmacophores from diverse ligands using the integrated FieldTemplater module
  • Find new chemical intellectual property using Cresset’s Blaze for ligand-based virtual screening directly from your desktop
  • Manipulate complex data within Forge using the new Column Script Editor to automatically modify or calculate molecular properties in the data table.

forge_10.3_screenshot
Forge V10.3 provides new features aimed at optimization of multiple activities simultaneously through an easy to use interface.