Presentations from Cresset’s user group meetings 2014

Cresset’s North American user meeting was held on June 11th. We were kindly hosted by Novartis in their Cambridge, MA facilities. The European meeting took place the following week on June 19th – 20th at Madingley Hall, Cambridge, UK.

Between them, the meetings were attended by a diverse group of computational and medicinal chemists from academia, industry and patent offices.

Links are provided below to the non-Cresset presentations we have permission to publish plus presentations by Cresset.

North American meeting – non-Cresset presentations

European meeting – non-Cresset presentations

Cresset presentations from North American and European meetings

Workshops

Both the North American and European meetings incorporated software workshops for delegates to receive hands-on software training on Torch with Activity Miner, Forge and Spark. Advanced workshops were also run for experienced users to learn more about recent new features in the software.

Contact us if you are interested in contributing to the scientific program of the 2015 Cresset user meetings.

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Delegates at European user group meeting at Madingley Hall, Cambridge, UK
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Delegates being guided through software workshop in North America
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January 2014 newsletter

Electrostatic environments around charged molecules: part 2 – dealing with proteins

Mark Mackey, our CSO, continues his article from last month by looking at using the same calculations to place a field on a protein. A couple of methods are discussed in order to find out how we can best generate field patterns for protein active sites. Read the article.

Focused screening library design

Discover an approach we have used successfully for the design of ‘focussed screening libraries’. Martin, our Director of Consulting Services, explains how we can help you enhance your expertise. Read the article.

Field Based Chemistry 2014

We’re finalizing the scientific programs for our North America and European user meetings. If you would like the opportunity to present please submit your abstract by February 28th. Workshops offering an introduction to Cresset software are available at both events. See details and register free at:

Advanced training for computational chemists

A one day advanced software training course will be held on June 18th at our training suite near Cambridge, UK. Aimed at computational chemists with some experience of Cresset software, the training will cover:

  • Finding detailed models of 3D binding sites using FieldTemplater
  • Developing reliable 3D-QSAR models
  • Analyzing selectivity with Activity Miner
  • Using available reagents to guide synthetic chemistry
  • Using multiple references to merge series or grow fragments
  • Developing internal fragment and reagent databases

Places are limited so please register early to avoid disappointment. See full details.

International Symposium on Compound Design Technologies

Guiding better decisions in drug discovery and development. March 19th, Tokyo and March 20th, Osaka. See full details and register free.

Webinar: Deciphering SAR around aromatics

March 25th. The first in a series of weinbars. During this webinar we will discuss ‘Deciphering SAR around aromatics’. Register free.

Review of Field Based Chemistry Europe 2013

Following on from the successful Field Based Chemistry North America last month, the scientific program of Field Based Chemistry Europe took place at Madingley Hall, Cambridge on 20th June 2013. A mixed program of speakers from academia and industrial organizations presented on a range of topics related to field based computational chemistry.

This blog gives a short overview of each speaker’s talk. Links will be added to the presentations as they become available.

In ‘Field points and structure based drug design’, Dr Gianni Chessari, Director at Astex Pharmaceuticals, presented the Astex approach to field points.

Dr Chessari described a case study of an X-linked inhibitor of an apoptosis protein in which field points were used to understand SAR and the ligand-protein interaction.

He concluded that a good understanding of the electrostatic interactions between ligands and proteins leads to efficient fragment optimisation and he noted that small molecule Cresset field points compare well with field points derived from ab initio methods.

Dr Mark Mackey, Cresset’s CSO, described ‘Upcoming features and future horizons’ for Cresset. He described the following new features:

  • The new XED FF3 released in Cresset products last year,
  • Activity cliffs and disparity analysis, available soon as a beta version,
  • The recently released BlazeGPU that gives a 40 fold speed increase to Blaze.

He also described the work that Cresset is doing on:

  • Calculating protein similarity
  • Calculating off-target effects using 3D descriptors and features.

Dr Mackay also touched on topics that Cresset are looking at for the future:

  • More work on analyzing protein fields.
  • Extending disparity analysis to qualitative models for SAR.
  • Extend off-target model work.
  • Building field based ADMET models.

In ‘Application of Forge and Spark to develop new drug candidates from lead compounds derived from network pharmacology models’ Dr Ben Allen of e-Therapeutics described how network pharmacology can help to identify drugs when nothing is known about their binding. His presentation described how they use networks to identify the protein footprint of compounds. They use the Cresset tools Spark and Forge for structural ligand-based bioisostere identification.

Dr Tim Cheeseright presented Cresset’s new Activity Miner module, which will soon be available as a plug-in for Torch or Forge. Activity Miner measures 2D and 3D similarity and compares it to activity to create a disparity score. The results can be displayed using four different views:

  • A colour coded disparity matrix that shows the disparity values for all pairs of molecules. This makes it easy to visually identify areas of high SAR.
  • A disparity table that shows the pairs with the highest disparity value. The table also includes physical activity and structure.
  • A cluster view that shows the molecules clustered by field similarity, but color coded by activity. This can be used to identify changes of activity within clusters.
  • An activity view that includes a focus compound. Other compounds are displayed, ordered by their similarity to the focus compound. These compounds are colour coded by their disparity, making it easy to identify the field changes that have resulted in the change of activity.

‘New drugs from old compounds’ described Re-Pharm, a new offshoot of Cresset. Re-Pharm uses Cresset software to find candidate compounds for reprofiling in order to find a new clinical use for an existing treatment.

After lunch, Dr Daniel Kuhn, of Global Computational Chemistry, Merck Serono presented, ‘How to convince your medicinal chemist – from 3D QSAR to scaffold hopping’. He described a 3D QSAR project using Forge and a scaffold hopping project using Spark.

Spark provided solutions intuitive to medicinal chemists which have been picked up for synthesis. He pointed out that good communication is essential to successful work with medicinal chemists. In particular, one of the strengths of Spark is being able to copy and paste solutions straight into chemical drawing tools such as ISIS Draw.

Dr Ian Wall from GlaxoSmithKline presented ‘Computational Approaches in fragment based drug discovery’ in which he described several in-house computational tools they have developed to help medicinal chemists get access to the maximum amount of data to inform their compound selection.

He outlined their approach to fragment based drug design and emphasised the importance of optimising fragments to maximise their activity before growing them.

In ‘The trend to outsource computational chemistry’ Dr Martin Slater, Cresset’s Director of Consulting, outlined the increasing fragmentation of the pharmaceutical industry and the decrease in R&D spend that have contributed to the increase in outsourcing of all aspects of drug discovery, including computational chemistry. He described a recent consulting project for Mission Therapeutics to produce a small compound library. Further reading: The trend to outsource computational chemistry; Cresset services.

María José Ojeda Montes of Universitat Rovira i Virgili presented ‘Conformational sampling tools’. She described a methodology they have been developing to explore the conformational space around leads. They found that the acceptable reliability for finding the bioactive pose decreased as the number of rotatable bonds increased above seven.

They hope in future to generate a database of pre-generated conformations of small molecules with less than seven rotatable bonds, which includes 70% of the small molecules of the Zinc database.

Dr Peter Hunt, Senior Research Investigator at Novartis, presented ‘Crystals, Co-formers and Cresset – adventures on the high C’s’. Co-crystals are a crystalline material consisting of 2 or more electrically neutral molecular species which are solids at ambient temperature. He gave the example of carbamazepine, which is very prone to forming co-crystals. However, the solvate furfural is toxic. The challenge is to take the toxic solute and to replace it with an acceptable co-former.

He noted that Cresset software generates ideas as to what might work and what might work better. They believe that co-crystal screening will grow in importance and the ability to rank acceptable co-formers will become a need.

The final presentation of the day was by Dr Andy Vinter, the founder and Chairman of Cresset. His talk, entitled ‘Kinetics versus thermodynamics – insight into protein function’ described the difference between the active β2AR/”G” vs the inactive β2AR. He described how studying the difference between the very similar active agonist and the inactive antagonist will reveal a lot of information and will be a useful test of the XED force field.

Dr Tim Cheeseright of Cresset closed the meeting by thanking the speakers.

March 2013 Newsletter

This month, Dr Rae Lawrence discusses a workflow that encompasses the elucidation of a reasonable binding mode pharmacophore template with forgeV10. She demonstrates how that template can be used for virtual screening to find diverse chemical series and how the results can ultimately be used for scaffold-hopping and lead optimization. Rae also highlights the experimental set up in blazeV10 and the pitfalls associated with multiple-molecule templates as the virtual screen seed. Read on to find out more.

forgeV10.1 Released

A new version of forgeV10, the computational workbench to understand SAR and design, is now available and is recommended for all users. Of particular note are:

  • the ability to apply differential weights to multiple reference molecules.
  • a new context sensitive menu on the 3D window.
  • support for viewing blazeV10 result files and legacy FieldView projects.
  • an improved workflow for molecule design.
  • improved pdb download and processing.

Contact us to upgrade or get a free evaluation.

Great Business Returns from Outsourcing

Concluding this series of blog posts, Dr Martin Slater explains Cresset’s very simple fee-for-service model for answering specific questions and addressing key issues in the discovery and early development phases of a new drug.

Cresset’s consulting team has demonstrated the value of outsourcing computational chemistry by delivering valuable results for many clients, proven in terms of patented scientific discoveries that have led to solid business returns.
Read the full article.

European User Meeting

On June 20th, speakers from Merck Serono, e-Therapeutics, Innovative Medicines Group, Trinity College, Dublin and Cresset will present during the scientific program in Cambridge, UK.

Workshop options for computational chemists:

  • Using cloud based virtual screening to find new leads.
  • Rapidly generating new scaffolds.

Workshop options for medicinal chemists:

  • Deciphering complex SAR.
  • Designing imaginative and effective compounds.

Register FREE now.

North American User Meeting

The scientific program includes speakers from Novartis, Broad Institute, Innovative Medicines Group, Utica College and Drexel University as well as Cresset.

Workshop option for computational chemists:

  • Rapidly generating new scaffolds.

Workshop option for medicinal chemists:

  • Designing imaginative and effective compounds.

Book early as we have limited places for this meeting on May 14th in Cambridge, MA. Register FREE now.

Meet us at ACS New Orleans


Meet our experts on booth 706 in the main exhibition hall or outside the COMP sessions at the Morial Convention Center. We’re also presenting on “Scaffold hopping”, “False false positives” and “How GPUs can find your next hit”; see when and where you can hear us.

Field Based Chemistry North America and Europe 2013

Welwyn Garden City, UK – 5th February 2013 – Cresset, innovative provider of chemistry software and services, announces Field Based Chemistry Europe 2013 and Field Based Chemistry North America 2013, two scientific meetings on the use of fields in the design and discovery of small molecules.

The events are of interest to researchers who want to: make the best possible compounds; shorten optimization processes; create or improve IP position by patent-busting or patent expansion; generate new leads, even in crowded therapeutic areas; develop lower-risk and lower-cost strategies for the discovery of new chemical entities.

Dr Robert Scoffin, CEO at Cresset says, “The Field Based Chemistry meetings build on our previous successful user group meetings. This year we look forward to welcoming individuals from commercial, research and academic organizations who are keen to explore what makes Cresset’s software and services unique.”

Field Based Chemistry North America 2013 takes place on May 14 at Novartis Institutes for BioMedical Research, Cambridge, MA. Speakers include Dr Patrick McCarren from The Broad Institute. Scientists and researchers are invited to submit abstracts for oral presentations by March 15, 2013. The meeting is offered free to delegates. http://www.cresset-group.com/fbcna2013/

Field Based Chemistry Europe is on June 20 to 21 at Madingley Hall, Cambridge, UK. Scientists and researchers are invited to submit abstracts for oral presentations and posters by March 15, 2013. The meeting is offered free to delegates. http://www.cresset-group.com/fbce2013/