April 2019 newsletter

Run Cresset calculations in the Cloud with Cresset Engine Broker™ and ElastiCluster

Paolo Tosco describes how to instantiate a cluster on Google Cloud (or any other cloud platform supported by ElastiCluster) and use it to run calculations with any Cresset desktop application, i.e., Forge™, Spark™ or Flare™, on any platform – Windows, Linux or macOS.

KNIME nodes V2.5.0 released

A new release of workflow components for the KNIME™ environment is now available. This includes nodes for the Machine Learning methods in Forge™, nodes for accessing Flare™ functionality through the Flare™ Python API, and a number of enhancements to existing components.

Electrostatic Complementarity™ scores: How can I use them?

Cresset’s new Electrostatic Complementarity method is a great way of visualizing the electrostatic interactions that a ligand can make with a protein. We also provide a score, so you can measure how complementary your molecule is to its binding site. When should you use the score, and for what? Mark Mackey provides the answers.

Ensemble docking in Flare™

Ensemble docking in Flare enables you to model protein flexibility by docking into multiple alternative active site conformations of the same protein in a single docking run. This gives you the ability to establish which protein conformation gives the best score for a given ligand.

In silico advantages for antibiotic development

Andy Smith details Cresset Discovery Services’ extensive experience working on established and novel anti-microbial targets. We understand the unique challenges of antibiotic development and bacterial resistance and can partner with your development team to reduce your development costs and decrease time to market for new antibiotics.

May 30 • Boston MA, USA

Efficient Drug Discovery Through Connected Chemistry: Effective Real-time Tracking of the DMTA Process

Chemistry in drug discovery, involving design, make, test and analysis, for modern pharmaceutical and biotechnology companies can involve many departments and external providers. This scientific seminar will discuss the challenges faced and present solutions to streamline the process.

June 20-21 • Cambridge, UK

Cresset User Group Meeting

Scientific program:

  • Invited presentations
    • Blazing Light: Combining Computational and Phenotype-based Drug Discovery to Restore Vision University College Dublin, Ireland
    • To be confirmed AbbVie, USA
    • Experiences in Establishing a Computational Chemistry Platform for Medicinal Chemistry Designers at Cancer Research UK – Manchester Institute CRUK MI, UK
    • Drug Repurposing: Computational and Cell-based Approaches University of South Australia, Australia
    • A Tale of Hide and Seek: Hit to Drug Candidate Institut Pasteur, South Korea
    • Unique insights into GPCR Allosteric Modulators Through the Application of Orthogonal Techniques Spanning Multiple Timescales UCB, Belgium
  • Cresset presentations
    • Torx: Connected Chemistry
    • Cresset Science: The Future Today
    • What’s New in the Cresset Desktop Applications: Flare, Forge, Spark
    • Introducing PickR: Generate Diverse R-groups for Hit Finding Libraries

Hands-on software workshops for computational, medicinal and synthetic chemists.

Previous event review, poster, presentations

• Review of symposium ‘Innovative Software for Molecule Discovery and Design’, New Delhi, India
• Presentations and poster from 257th ACS National Meeting:

March 2019 newsletter

Rapid interpretation of patent SAR using Forge™

Tim Cheeseright explains how Forge can be used to rapidly convert patent data into actionable insights of SAR with minimal human intervention and time.


Building regression models in Forge™

New Machine Learning methods in Forge significantly expand the range of available QSAR model building options, giving you more opportunities to build a predictive model useful in project work. Our latest web clip demonstrates how to generate a QSAR regression model.

View this and other video clips.


Application of Spark™ to the discovery of novel LpxC inhibitors

Novartis Institutes for Biomedical Research recently published the paper ‘Application of Virtual Screening to the Identification of New LpxC Inhibitor Chemotypes, Oxazolidinone and Isoxazoline’. Suneel Kumar highlights how, in this paper, a traditional scaffold hopping experiment using Spark led to the identification of novel oxazolidinone and isoxazoline LpxC inhibitors active on Gram negative bacteria.


How do I turn my biology insight into a novel therapeutic?

Caroline Low looks at some of the ways that in silico technology can be used to translate your ideas into chemical tools. Optimizing the drug-like properties of these early hit compounds will put you on the road to defining a lead series and onwards to nominating a drug candidate for clinical studies.


Did you know ….

  • Flare
    • You can download multiple proteins from the RCSB at the same time
    • There is an Atom Pick panel so you can perform advanced atom pick operations
  • Flare, Forge, Spark
    • When working with large datasets you can tag interesting molecules to keep track of them

Upcoming events

  • April
    • 31 March-April 4, 257th ACS National Meeting, Orlando, FL, USA
    • 4, UK QSAR Spring Meeting, Cambridge, UK
    • 4-5, Protein-Protein Interactions, Leeds, UK
    • 5, Applied Pharmaceutical Chemistry, Cambridge, MA, USA
    • 9-11, Drug Discovery Chemistry, San Diego, CA, USA
    • 10, SCI-RSC Workshop on Computational Tools for Drug Discovery, Birmingham, UK
    • 10, Innovative Software for Molecular Discovery and Design, Bangalore, India
    • 12, Big Ideas for Big Data in Drug Discovery, London, UK
  • June
    • 20-21, Cresset User Group Meeting, Cambridge, UK
      • Scientific program, including speakers from:
        • Institut Pasteur, South Korea
        • University of South Australia, Australia
        • AbbVie Inc., USA
        • Keio University, Japan
        • University College Dublin, Ireland
        • Cancer Research UK – Manchester Institute, UK
    • Which workshop will you attend?

See these events and more.

February 2019 newsletter

Comparing Forge’s command line utility to Blaze – which one should you use?

Here at Cresset we’re very interested in ligand-based virtual screening – it’s been a focus of the company ever since we started more than seventeen years ago. One of the things our customers ask from time to time is which application should they be using to do virtual screening? The simple answer is that there are two: Forge and Blaze. Mark Mackey explores the differences between these applications and discusses where each should be used to best effect.


Designing new molecules in a web browser

Last year we discussed our research aimed at re-imagining molecule design to bring the best of 2D and 3D technologies together in a collaborative environment. Tim Cheeseright, describes how the project, code-named TorchWeb, is progressing and is now on the count down to a beta release, expected in the early summer of this year, with an initial release to follow in the autumn.


Publication: Electrostatic complementarity as a fast and effective tool to optimize binding and selectivity of protein-ligand complexes

We are delighted to announce that our work on Electrostatic Complementarity has just been published in the ‘just accepted’ section of J. Med. Chem. This revolutionary technology was introduced in Flare V2.0 and is receiving a lot of attention across our customer base.


Application of Spark in the discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction

Bayer AG recently published an interesting paper on the discovery of potent and selective SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction. Suneel Kumar, Applications Scientist, explores what the paper reveals about the use of Spark in this project.


Did you know ….

Flare

  • All Flare functionality can be accessed from the command line: see Gitlab for more information.

Flare and Forge

  • Use keyboard shortcuts 1, 2 and 3 to change the bond order when hovering over a bond in the Forge, Spark and Flare molecule editor. It’s quicker than clicking on the bond!
  • You can convert numeric activity values to categorical activity values. Right-click on the Activity column header and choose ‘Activity & Model Manager’, then choose ‘Convert number to category’ under ‘Units’. This is useful for building machine learning classification models.•

Forge

  • New Machine Learning methods in V10.6 significantly expand the range of available QSAR model building methods. QSAR classification models are useful to analyze categorical activty data, i.e., when the biological data take the form of qualitative labels (e.g., High, Medium and Low) or of activity ranges (e.g., % of inhibition data). See how to generate a QSAR classification model.

Upcoming events

March

April

June

January 2019 newsletter

Forge V10.6 released

We are delighted to announce the availability of Forge™ V10.6, our powerful computational chemistry suite for understanding structure-activity relationship (SAR) and new molecule design. Giovanna Tedesco details the focus of this release, which is on new and improved methods to generate robust Quantitative Structure-Activity Relationship (QSAR) models with strong predictive ability. See the new features of Forge V10.6 in this web clip.

Existing users are encouraged to upgrade to Forge V10.6 at their earliest convenience, and to download the Forge V10.6 keyboard shortcuts and Forge V10.6 Molecule Editor keyboard shortcuts.


Forge Design: New name, familiar environment

Forge Design is a new licensing level of Forge™ for medicinal and synthetic chemists. It replaces Torch™ and benefits from the familiar GUI, but with V10.6 enhancements. Tim Cheeseright explains what Torch users can expect from Forge Design, including new functionality, how Forge Design compares to Torch and Forge and the simplicity of upgrading to new releases.


Modeling the intricacies of molecular recognition: Make ‘smart antibodies’ into biologics

Antibodies are fantastically versatile molecular recognition engines, capable of creating artificial enzymes in response to recognized interactions. Similarly, enzymes depend on molecular recognition for catalysis. Martin Slater describes Cresset Discovery Services’ depth of experience in modeling molecular recognition scenarios, stretching back to the early nineties.


Cresset User Group Meeting 2019 registration open

Cambridge, UK • June 20-21

“The Cresset team and I would be delighted to welcome you to the Cresset User Group Meeting 2019.

As well as invited presentations from leading researchers in our field, Cresset scientists will present our latest science and showcase upcoming applications to help your chemists design the best molecules as efficiently as possible.

Whether you are new to Cresset, have been with us from the beginning, or are just intrigued to find out more about the solutions we offer, I hope you can join us for the scientific program and hands-on software workshops.”

Dr Robert Scoffin, CEO

Register for Cresset User Group Meeting 2019

December 2018 newsletter

CEO end of year message 2018

“As we near the end of the year I’ve been reflecting on the progress we’ve made. During 2018 we’ve seen major developments in Cresset Discovery Services, in software development, and in our application science team in particular, but wherever I look in the company there are exciting activities and new faces. Here are a few highlights of the past year.” Dr Robert Scoffin, CEO


Sneak peek at Forge V10.6: Model building focus and much more

While the development team is busy giving the finishing touches to Forge V10.6, Giovanna Tedesco reveals a sneak peek of what is new in this release, including: improved predictions through new models, generating qualitative models on small datasets, more responsive GUI for larger projects, and improved interface to Blaze for virtual screening.


Get the very best availability information on which reagents to order for Spark

Download the latest release of the Spark reagent databases using the Spark Database Updater widget from the Spark GUI or the command line ‘sparkdbupdate’ binary (instructions on the installing Spark databases page).


Enhancements in Flare V2 allow our scientists to spend more time on your design and analysis project

The release of Flare V2 brings quicker analysis of new design ideas and more automation of workflow processes. Andy Smith, Discovery Services Scientist, explains the advantages that Flare V2 brings to Cresset Discovery Services customers, including more time spent on high-value design and analysis work.


CEO end of year message 2018

Dr Robert Scoffin, CEO

As we near the end of the year I’ve been reflecting on the progress we’ve made. During 2018 we’ve seen major developments in Cresset Discovery Services, in software development, and in our application science team in particular, but wherever I look in the company there are exciting activities and new faces. Here are a few highlights of the past year.

Our landmark structure-based design tool, Flare™, has been expanded to include Electrostatic Complementarity™, ensemble docking and much more, making it a truly powerful design environment for medicinal chemists. Not forgetting our computational chemist audience, we’ve also added a Python API, making Flare a new playground for computational chemists, scripters and developers.

The year also saw us reveal an exciting new development project: a web-based platform for small molecule discovery. In case you missed the announcement, have a look at this sneak peek at next generation collaborative 3D design. This project, combined with our collaboration with Elixir Software, will deliver a platform that will radically increase the efficiency of drug discovery by managing, analyzing and reporting all processes within and between drug discovery projects. Further details will be announced next year.

One of the highlights of any year is always the many customer interactions we enjoy – not least at our annual Users’ Group Meeting. In June we were honoured to welcome delegates and presenters from all over the world to share their research progress and scientific successes. Even if you were not able to attend, many of the presentations are available online. As always, delegates expressed their appreciation of the science presented and the hands-on workshops. You are warmly invited to join us for the 2019 UGM on June 20-21 in Cambridge, UK.

As our software development and commercial activities increase, we’re delighted to have welcomed several new team members, including Dr Andy Smith who has joined Cresset Discovery Services as Discovery Services Scientist, based at BioHub, Alderley Park, UK.

I’d like to sincerely thank you, our customers, partners and the Cresset team, for all of your input and support. We look forward to delivering more outstanding applications to enhance your research in 2019 and beyond.

November 2018 newsletter

New free licensing options of Flare for structure-based design

We are delighted to announce the availability of two free licensing options of Flare, Cresset’s structure-based design application:

  • Flare Viewer enables you to easily visualize and analyze your protein-ligand complexes using our proprietary electrostatics to design new ligands, and communicate your ideas with high quality graphics and pictures. See it in action in this short video.
  • Flare for Academics, specifically designed for academic users, is a user-friendly environment where academic users can easily develop and test their ideas and methods. It extends on the functionality of Flare Viewer to provide an excellent platform for drug discovery, with a focus on ligand design and electrostatics.

Python extension enabling Jupyter Notebook integration in Flare released

Paolo Tosco describes a number of features that have been implemented into the recently released Python extension for Flare.


Which macrocycle should I try first? Picking the best linkers with Flare and Spark

See how the new Electrostatic Complementarity™ maps and scores in Flare™ are used to help the post-processing of a Spark™ macrocyclization experiment.


A measure of success: Being named on patents and references

We answer one of the most common questions asked of every contract research organization: What have you produced?’ or, in other words, ‘What evidence is there that you will provide value for our money?.


Presentations and poster from recent events


Upcoming events

  • 6 December: Trends in Medicinal Chemistry, London, UK
  • 13 December: Genesis 2018, London, UK
  • 20-21 June: Cresset User Group meeting 2019

See all events.

October 2018 newsletter

Sneak peek: PickR to select electrostatically diverse monomers for libraries

PickR will be a new command line application to generate diverse R-groups for library design. Tim Cheeseright takes a peek at the results from using PickR to cluster 1000 amino side chains.


Make the molecules that matter

Watch our short video to see how Cresset Discovery Services works alongside your chemists to solve problems, provide fresh ideas, remove roadblocks and add direction and insight.


RDKit User Group Meeting review

Paolo Tosco reviews the RDKit UGM – one of his favorite scientific events of the year. From his presentation about the integration of RDKit in Flare, our structure-based design tool, and in particular on its usage from Python through the built-in Jupyter Notebook interface, to what’s new in RDKit, GSoC RDKit-MolVS integration, open source programs built on the RDKit, RDKit in the modern biotech and cheminformatics problems – Paolo discusses them all.


Introducing Andy Smith, Discovery Services Scientist

Andy Smith has joined Cresset Discovery Services, where he will work on customer projects. Read about his computational chemistry journey so far, including work on GPCRs, structure-based design, anti-infectives, oncology and crop protection.


Recent news


Citations

  • In Silico Discovery of a Small Molecule Suppressing Lung Carcinoma A549 Cells Proliferation and Inducing Autophagy via mTOR Pathway Inhibition, Mol. Pharmaceutics, Article ASAP, DOI: 10.1021/acs.molpharmaceut.8b00996
  • A Structure- and Ligand-Based Virtual Screening of a Database of “Small” Marine Natural Products for the Identification of “Blue” Sigma-2 Receptor Ligands, Marine Drugs. 2018; 16(10):384
  • Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates, International Journal of Medicinal Chemistry, vol. 2018, Article ID 9139786, 11 pages, 2018

See these and other citations.


Upcoming events

November 2018

  • 31 October-2 November, AusBiotech 2018, Brisbane, Australia
    • Meet us at booth 45
  • 1-4, Informatic Tools in Drug Discovery and Delivery, Patiala India
    • Workshop: Electrostatic Complementarity™ as a New Approach to Visualize and Predict Activity
  • 11-13, 14th German Conference on Chemoinformatics, Mainz, Germany
    • Poster: Predicting Activity Using the Electrostatic Complementarity™ of Protein-ligand Complexes
  • 20, Innovative Software for Molecular Discovery and Design, Lucknow, India
  • 22, Innovative Software for Molecular Discovery and Design, Hyderabad, India
  • 30, MGMS Young Modellers’ Forum, London, UK

2019

See all events.

Cancer Research UK Manchester Institute enhances toolkit for computational and medicinal chemists with Flare for structure-based drug design

Cambridge, UK – 18th October 2018 – Cresset, innovative provider of software and contract research services for small molecule discovery and design, is pleased to announce that Cancer Research UK Manchester Institute (CRUK MI), has licensed Flare for fresh insights into structure-based drug design.

“Putting easy-to use and visually driven structure-based design software in the hands of our medicinal chemists will empower them to deliver the next generation of cancer therapeutics more efficiently,” says Professor Caroline Springer, Director of the Drug Discovery Unit, CRUK MI. “These tools provide a common interface to further integrate our medicinal and computational chemistry expertise, and we are particularly excited that we will be able to gain immediate feedback on where to optimise the ligand-protein interactions by visually assessing how protein and ligand electrostatics complement each other.”

“Having licensed our ligand-focused applications, Spark™, Forge™ and Torch™, to CRUK MI for a number of years, we are delighted that this leading research institute, has added Flare™ for structure-based design,” says Dr David Bardsley, Commercial Director, Cresset.

Cresset’s innovative Electrostatic Complementarity TM maps and scores provide rapid feedback on new molecule designs. Green: good electrostatic complementarity. Red: electrostatic clash.

 

Cresset and Elixir collaborate to deliver efficiencies to the Design Make Test Analyze (DMTA) Cycle

Cambridge, UK – 15th October 2018 – Cresset, innovative provider of software and contract research services for small molecule discovery and design, and Elixir Software, provider of real-time workflow tracking applications, have formed an alliance whereby the combination of their technologies will form the basis of a new groundbreaking application, which will radically increase the efficiency of drug discovery by managing, analyzing and reporting all processes within and between projects.

“The modern paradigm in drug discovery is highly collaborative, both internally and externally, with design partners and CRO’s for instance. Key to making this paradigm efficient is effective real-time communications and the ability to manage and track all aspects of the Design, Make, Test, Analyze (DMTA) process.”, says Dr Robert Scoffin, CEO, Cresset.

“Elixir bring their cloud-based chemTraX platform to the collaboration; a highly visual DMTA workflow application for hypothesis capture, compound design prioritization and synthesis tracking. This will deliver improved/increased efficiencies wherever new molecule discovery is carried out.”, says Dr Paul Faulder, CEO, Elixir Software.

“Cresset bring a wealth of experience and expertise in the analysis and design of novel chemical entities. By combining these technologies, it is our ultimate vision to create a platform that enables efficient, modern drug discovery on a global scale and focusing on interactive communication and seamless collaboration amongst members of the discovery team.”, says Dr Tim Cheeseright, Director of Products, Cresset.