Torch V10.4 released

The latest version of Torch, our 3D molecule design tool for medicinal chemists and synthetic chemists is now available. Torch uses Cresset’s description of a molecule’s shape and electrostatic character to help you understand the root causes of activity and use this to design new compounds. V10.4 has new functionality to aid decision making around new designs and an enhanced user interface.

Highlights

  • New Multi-parameter Optimization (MPO) options including condensing many activity and physicochemical properties into a single score representing the fit to the project profile
  • Color molecules and table cells using the MPO score (Figure 1)
  • Color molecules in the protein binding site using activity or logP or other physicochemical properties
  • View molecules as Tiles with selected data
  • Divide your dataset into different Roles and add tags to label important compounds or subsets.

torch_10.4_new_features
Figure 1: The colorful new Tiles view and histograms in TorchV10.4

 

Torch V10.4 has hundreds of improvements on the previous versions that will enhance your experience. If you are currently a user then get in touch for download links. If you haven’t tried Torch before get your free evaluation.

Multi-parameter optimization in Torch

radial_plot_concept_torch10.4

Figure 2: Enhanced Radial Plot

In Torch V10.3 the Radial Plot was introduced to provide a graphical representation of numerical data. In particular it created a simple picture to show how a molecule fits the physicochemical profile of a project with the idea that parameters are within an ideal range, an unacceptable range or somewhere in between. V10.4 enhances this representation by combining all the scores in the Radial Plot together into a single number scaled between zero and 1 (Figure 2).

Thus compounds with a radial plot score of 1 fit the project profile perfectly while those with zero lie outside the desirable property space in all aspects. Since not all properties are equally important, Torch enables a weighting factor that can be applied to each property (Figure 3). The weight is used to scale the contribution to the final score. This is useful when you want to focus on one property more than another, for example you are prepared to have a non-ideal value for MW if the logP and TPSA are within the ideal range or you want a visual representation of that property but not have it count towards the score.


Figure 3: The configuration of the Radial Plot now includes a weight to apply to each property in combining the properties into a single score.

Coloring of molecules in the 3D window now has options to apply a color scale based on any numerical property in the molecule table including the new radial plot score (Figure 4). This simple feature requires you to define how the scale should be applied to the numbers (by means of the Radial Plot property configuration). Once this is complete you are able to investigate how the 3D alignment and shape of molecules varies with the individual physicochemical properties and the overall project goals.


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Figure 4: Nine DPP4 active molecules colored by activity (left) and Radial Plot Score (right). Green represents a better fit to the ideal values for the two properties (activity, radial plot score). In this case the most active compounds (top row) do not fit the overall project profile as well as those with lower activity (bottom row).

 

Helping SAR interpretation – molecule organization, tagging and plotting

This release enhances Torch’s ability to study SAR in multiple ways. You can now divide molecule datasets into separate sections, tag any molecule with an arbitrary text based label benefit from improved plotting capabilities to study numerical data and select molecules.

Molecule roles were introduced in the first release of Forge to enable it’s 3D-QSAR functionality. However, we found that we use this functionality extensively even when we are not interested in 3D-QSAR, for example, to group compounds into series or split out those that are designs from those that have been tested or are out for synthesis. We use molecule Roles (Figure 5) to help cluster datasets using 3D similarity with Activity Miner, to look at different sub-groups, as well as for the original purpose – 3D-QSAR. In bringing this functionality to Torch we are sure you will find it equally useful.


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Figure 5: Tiles view of molecules split by Roles showing Radial Plot, Notes, and Tags on each medium sized tile.
Molecule Roles enable the categorization of molecules into single bins. To complement this, molecule Tags have been introduced to enable the labeling of molecules across multiple roles with any number of arbitrary labels. We tag compound sources, stereochemistry, designed vs tested, personal favorites, R-group variations and different series. When combined with the ability to filter the molecules based on these tags and the new ability to filter on substructures you get excellent flexibility to investigate even large SAR datasets.

Plotting histograms and scatter plots is now possible with Torch V10.4 (Figure 6). This simple enhancement comes with interactive selection of molecules and significantly improves the study of molecule properties across a dataset or within a role. For example, selecting a molecule in a scatter plot of Activity vs logP highlights the selection in a histogram of MW. Combined with the display of the selected in the 3D window it provides added flexibility in SAR analysis.


interactive_plots_torch_10.4
Figure 6: Scatter plots and Histograms in Torch V10.4 are interactive, selecting in one graph highlights the same molecules in other graphs.

Tiles view

To complement Tags and Molecules Roles we have introduced the Tiles view of molecules that has been so popular in Spark. This view presents any of the data that is in Torch on a tile and enables you to focus on the information that is important to you at the same time as seeing as much of the dataset as you can.

New models of activity

In Forge, Activity Atlas models have been introduced as a new way of summarizing your SAR in a simple yet detailed 3D view (Figure 7). In Torch these models act as templates to design new molecules. They are present in the 3D window and also in the editor to enable the interactive design (in 3D) of molecules that explore new regions of SAR or help you focus on maintaining activity while perfecting your macro-properties. We are confident that Activity Atlas models will transform your view of molecule design.


Figure 7: 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.

 

Try Torch V10.4

To try the new features in Torch V10.4 simply download a free evaluation or contact us for download links.

Computational Chemistry Software Suite Chosen by Medical Research Council Technology

Medical Research Council Technology (MRCT) has chosen to license Cresset’s computational chemistry software suite.

“The decision of MRCT to work with Cresset’s computational chemistry software suite demonstrates the value and insight our products bring to researchers,” says Dr. David Bardsley, Cresset’s Commercial Director.

Dr. Kristian Birchall of MRCT says, “We are pleased to be working with Cresset’s software. This provides us with intuitive molecule design, a powerful ability to understand SAR and design plus a fresh way for generating novel and diverse structures for our projects.”

Dr. Bardsley adds, “Cresset’s software works at the meeting point of chemistry and biology, giving chemists a way of understanding their molecules in terms of biological activity. Our technology and services are providing companies with the right information, wherever they sit in the drug design workflow.”

A Practical Introduction to Using Cresset’s Tools for Imaginative Molecule Design

Cambridge, UK – 18th September 2013 – Cresset, innovative provider of chemistry software and services, is holding a one day introduction to using computational tools for imaginative molecule design at Centre de Serveis Científics i Acadèmics de Catalunya (CESCA), Barcelona, Spain on 31st October.

“Delegates will explore how to rapidly generate new scaffolds and decipher complex SAR using the Spark and Forge software suites. Each session will be hands on so everyone will have the opportunity to work with our software personally,” says Dr Tim Cheeseright, Cresset’s Director of Products.

Dr Cheeseright adds, “We are delighted that María José Ojeda Montes, Universitat Rovira i Virgili will present on ‘Conformational Sampling Tools’ and Dr Mark Mackey, Cresset’s CSO will give insight on ‘Beyond simple similarity: Understanding the Route Cause of Activity’.”

Switching Series

When researchers find their promising lead series facing IP issues, they are faced with a tough decision. Do they change series—possibly to a candidate that doesn’t show the same level of activity against the target—or do they spend a great deal of time and money screening the totality of the corporate database for a new prospect? In this situation, scaffold hopping and virtual screening are effective and efficient ways to identify a new series to move the project forward.

Read the full article by Martin Slater and Katriona Scoffin in Drug Discovery and Development Magazine.

Torch Brings the Next Generation of Molecule Design to the Desktop

Protein’s eye view gives clear insights into the causes of biological activity

Welwyn Garden City, UK – 25 October 2012 – Cresset, innovative provider of software and services, announces the release of Torch, a complete desktop molecular design and 3D SAR tool for medicinal chemists.

Torch uses molecular fields to show the binding patterns of your compounds. This protein’s eye view gives clear insights into the causes of biological activity.

Working with Torch, medicinal chemists can see how to optimize the shape and electrostatic properties of their series, and rapidly identify the best next molecule to synthesize.

Cresset CEO, Dr Robert Scoffin said, “We believe that molecular fields are the most intuitive way of assessing biological activity. We would like every chemist to access the power of fields so that they can truly understand the mechanisms by which their leads interact with targets. Torch is such an easy to use desktop tool that it brings these insights within the reach of every medicinal chemist.”

torchV10 screenshot

Torch is a complete desktop molecular design and Structure Activity Relationship (SAR) tool that brings the power of fields within the reach of every chemist.

Medicinal chemists, research managers, academics and computational chemists who want to find out more about Torch can register for a free introductory webinar.

Torch Released

We are delighted to announce the release of Torch, the next generation of FieldAlign, an intuitive 3D molecule designer. Torch brings new capabilities to medicinal chemistry desktops while maintaining our focus on easy to use, easy to learn software that produces meaningful results within minutes.

Existing FieldAlign users can upgrade to Torch for free. If you have not already received your new license file then please let us know. If you’re new to our molecule design software you can get a free one month evaluation here.

In common with Forge and Spark, Torch uses the next generation of our proprietary XED force field to describe molecules and their interaction from the protein’s view point. Using Torch gives medicinal chemists a unique insight into how molecules relate to each other and to the target protein, enabling a deep understanding of structure activity relationships. However, understanding is only half of the equation. Torch brings a powerful molecule editor and sketcher that chemists use to design their next molecule. The editor provides immediate feedback on each design giving a rapid progression of idea to synthesis.

torchV10
Specific additions in Torch are:

  • New molecular mechanics force field (XED3).
  • New protein importer to read and process pdb files into protein and reference molecule.
  • Download pdb files directly into Torch and view protein-ligand interactions.
  • Display and use Forge QSAR models in the scoring of molecules.
  • Improved molecule reading to give fewer clicks and more intuitive operation.
  • Measure distances, angles and torsions, automatically display intramolecular H-bonds and atomic clashes.

Forge Introduction and Training

Our recent series of Forge training sessions has proved popular. Here we give you the recorded session to view at you leisure. The presentation includes an introduction to Cresset’s technology followed by worked examples of using Forge to generate ligand alignments and 3D QSARs. If you would like to follow along then please contact us for a download link to all the files used in the presentation.

You can also contact us to request a personalised Forge training session.

Fast Computational Method for Fragment Growing and Joining Using Molecular Fields

Our presentation on ‘Fast Computational Method for Fragment Growing and Joining Using Molecular Fields’ by Dr Martin Slater, Director of Consulting, builds on the fragment growing article we published in November 2011.

To view Martin’s presentation, which was made at the CHI Structure Based Design conference in Boston MA, June 2012 click here:

SBDD_2012

Cresset Launches Forge and Range of Next Generation Chemistry Software

Welwyn Garden City, UK (28th May 2012) Cresset, innovative provider of software and services for molecule designers launches Forge a powerful computational suite to understand SAR and design. Forge gives computational chemists control and insight into activity data enabling the planning and direction of projects with confidence. Forge uses the shape and electrostatic character of molecules to create qualitative and quantitative 3D models of activity that are visually stimulating and easy to communicate.

Forge takes advantage of Cresset’s’ patented ligand comparison method to align, score and compare molecules from a biological view point. Cresset’s technology has been tried and tested in hundreds of projects from virtual screening to compound design. Forge is used to: decipher complex SAR and communicate the results; design better molecules based on predictions which can be trusted; prepare detailed pharmacophores; virtually screen 10 000 compounds on the desktop; and generate ADME and off target activity profiles. The powerful capabilities afforded the user by forgeV10 are available through locally installed software or through Cresset Consultancy Services.

Meeting the needs of computational and medicinal chemists, Cresset’s new suite of next generation chemistry software comprises: Forge a powerful computational suite to understand SAR and design; Torch an intuitive design and 3D SAR tool for medicinal chemists; TorchLite a free 3D molecule viewing, editing and drawing tool; Blaze an amazing ligand based virtual screening tool; Spark an exciting and powerful way of generating novel and diverse structures.

Cresset CEO, Dr Robert Scoffin said, “We are excited to bring to market these powerful tools to help companies maximize the potential of their projects. Some of the applications have simply been renamed but others have changed significantly and now include exciting new features. The release of Forge as the lead off application in the Cresset pro v10 suite is a milestone in the provision of excellence in computational chemistry software.”

Scientists interested in Cresset’s next generation software can download free demos from the company’s website.

For more information about Cresset’s software and service solutions please visit Cresset’s website, alternatively email Cresset. You can also follow Cresset on Twitter @Cressetgroup or join the LinkedIn group..

Forge Sneak Peek

We’ve been working steadily over the last six months to improve on our offering to Computational Chemists and other power users. The result is Forge, a new application that combines all the features of FieldAlign and FieldTemplater into a single new package and adds a heap more of the functionality you’ve asked for. We are really pleased with the result and as we near release we thought we would let you in on the secrets that are coming soon.

The primary role of Forge is to help with decoding structure activity relationships and generating new molecule designs with meaningful activity predictions wherever possible. On the design side we’ve revamped the molecular editor to give you the flexibility to design molecules using fields in an interactive environment. Take a look at the screenshot below:

Forge Molecular Editor

The screenshot shows the new drawing buttons on the left with ring templates which will please all those that asked for them and make drawing far less painful. There is a new button on the right “Align” will align the molecule that is present in the editor to the reference molecule giving you immediate feedback on a new design and giving you the ability to manually edit alignments. We call this “score while you draw”!

To enhance the understanding of structure activity relationships in your molecules we have introduced automated analysis of field patterns using a QSAR method and new alignment methods to give you more ligand centric views as opposed to the protein centric view that we have traditionally generated. The QSAR that we are introducing is a completely new 3D method that uses the field points around your ligands as sampling points for the field of a ligand. In effect we generate a irregular, non-lattice grid around the ligands which is then used to generate field samples on every molecule in the training set. Using PLS acrosss this dataset gives an indication of which regions of the field are contributing to the observed changes in activity but also generates a way of predicting activities for compounds of unknown activity. The QSAR model that you create can be exported to be used by others or used to help the design process including in the “score while you draw” feature. The QSAR is completely integrated into Forge with all the statistics that you would expect from a method of this type (see the screenshot below for an example). Of course 3D QSAR is not a panacea but in our hands this methods has greatly enhanced many of the customer projects that we have worked on.

Forge screen shot showing model information

Underlying these functionality improvements is a new version of our XED molecular mechanics force field that introduces some fundamental changes as well as field pattern improvements. The biggest change in the force field is the introduction of a completely analogue nitrogen atom type that can transition from planar to pyramidal depending on the degree of hydbridisation with surounding atoms.

Lastly, Forge is firmly a Cresset application and comes with the intuitive user interface that you have come to expect from us, plus  a comprehensive wizard to guide you through the process of setting up experiments.

Forge showing a FieldAlign type of interface
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