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.

September 2018 newsletter

Integrating Jupyter Notebook into Flare

Take a sneak peak at Paolo Tosco’s work to integrate the Jupyter Notebook into Flare including the example workflow that he presented at the 7th RDKit user meeting.


Using Python in Flare to find common contacts in Flare

Tim Cheeseright takes a look at using Flare to automatically highlight the difference in binding site residues for two PDE5 ligands.


See Flare V2 new science and functionality in action

Following the launch of Flare V2 in June, this video demonstrates the fully featured science driven application which enables you to learn more about your protein-ligand systems.


Spark reagents databases

Monthly updates to the Spark reagent databases give you access to the latest reagent availability information, helping you make informed choices between Spark results. Download the latest version using the Spark Database Updater. Command line options are also available.


Artificial Intelligence and machine learning: Where’s the intelligence?

Andy Smith, Discovery Services Scientist, discusses the distinction between AI and machine learning, mining big data in drug discovery, prediction and understanding for small data sets, and how the real intelligence lies with the operator.


Review of XXV EFMC International Symposium on Medicinal Chemistry

With three separate scientific tracks: Therapeutic Areas, Technologies and Chemical Biology, it was impossible for the 800 plus delegates to see everything, but the busy schedule meant that there was something for everybody. Martin Slater reviews first disclosures, GPCRs and other highlights.


Citations

  • Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study, Molecules 2018, 23, 1368.

See this and other citations.


Upcoming events

October

  • 8th-9th, 3rd RSC BMCS Medicinal Chemistry Symposium on Macrocycles, Stevenage, UK
    • Poster: Rapid and Accessible In-silico Macrocycle Design: Application to BRD4
  • 9th-10th, ELRIG Drug Discovery for Small and Large Molecules, London, UK
  • 9th-11th, Chem-Bio Informatics Society, Tokyo, Japan
    • Seminar: Predicting Biological Activity Using the Electrostatic Complementarity of Protein-ligand Complexes
    • Poster P2-06: Rapid and Accessible In-silico Macrocycle Design
  • 10th-12th, Bio Japan, Yokohama, Japan
  • 18th, Symposium on Streamlining Drug Discovery, Cambridge, MA, USA
  • 23rd, Symposium on Streamlining Drug Discovery, San Diego, CA, USA
  • 24th, Synthesis in Drug Discovery and Development Symposium, Alderley Edge, UK
  • 25th, Symposium on Streamlining Drug Discovery, San Francisco, CA, USA
  • 31st-2nd November, AusBiotech, Adelaide, Australia

Date for your diary

  • Cresset User Group meeting 2019, June 20th-21st

See all events.

August 2018 newsletter

Investigating the SAR of XIAP ligands with Electrostatic Complementarity maps and scores

In this case study, we used the Electrostatic Complementarity maps available in Flare to investigate the protein-ligand electrostatic interactions and the SAR of a set of inhibitors of the X-linked IAP (XIAP)-caspase protein-protein interaction. Electrostatic Complementarity scores calculated with Flare were used to quantitatively model XIAP-BIR3 pIC50.


Outstanding new 3D graphics in Spark V10.5.5

A new patch level release of Spark™, our scaffold hopping and bioisostere replacement application, is now available. Spark 10.5.5 includes improvements to the look and feel, rendering and performance of the graphics of the 3D window. Customers will receive the download link soon. If you’re not currently a Spark customer, request your free evaluation.


Modeling ‘big’: Applying the XED force field to biologics

Cresset is well known for powerful and accurate ligand-centric modeling, and Flare has established our methods for protein-ligand interactions. Work on GPCR modeling and viruses demonstrates the effectiveness and potential of Cresset technology for protein-protein interactions. Martin Slater, Director of Consulting Services, discusses the successes and challenges of modeling ‘big’ – applying Cresset’s XED force field to biologics.


Presentation from 256th ACS National Meeting

See the Rapid and accessible in silico macrocycle design presentation Rob Scoffin presented in the COMP Division at the 256th ACS National Meeting.


Citations

  • Exploring Modifications of an HIV-1 Capsid Inhibitor: Design, Synthesis, and Mechanism of Action, Journal of Drug Design and Research
  • Field Template-based Design and Biological Evaluation of New Sphingosine Kinase 1 Inhibitors, Breast Cancer Research and Treatment
  • Identification of Potentially Potent Heme Oxygenase 1 Inhibitors through 3D‐QSAR Coupled to Scaffold‐Hopping Analysis, ChemMedChem
  • Kinetic Characterization of Novel HIV-1 Entry Inhibitors: Discovery of a Relationship between Off-Rate and Potency, Molecules

See all citations.


Upcoming events

September

  • 2nd-6th, XXV EFMC International Symposium on Medicinal Chemistry, Ljubliana, Slovenia
    • Meet us on stand 32 and see our poster ‘Rapid and Accessible In-silico Macrocycle Design-Application to BRD4’
  • 10th-12th, 7th RSC/SCI Symposium on GPCRs in Medicinal Chemistry, Verona, Italy
    • Meet us in the exhibit area and see our poster ‘Summarizing and Understanding SAR and Activity Cliffs in GPCRs’ (P33)
  • 16th-20th, 22nd European Symposium on Quantitative Structure-Activity Relationship, Thessaloniki, Greece
    • Oral: Predicting Activity Using the Electrostatic Complementarity of Protein-ligand Complexes
    • Poster: Can I Make This Into a Macrocycle? Effective Methods for Fragment Growing, Joining and Cyclization
  • 17th-18th, Medicinal Chemistry Summit, Boston, MA, USA
  • 19th-21st, RDKit User Group Meeting, Cambridge, UK
  • 26th, The Best of Both Worlds: Innovation, Collaboration and Synergy between CROs and their Client Partners, Stevenage, UK
    • Poster: Predicting Activity Using the Electrostatic Complementarity™ of Protein-ligand Complexes
  • 26th, UK QSAR Fall Meeting, Oxford, UK
  • 28th, BioCap, Alderley Park, UK

October

  • Symposium on Streamlining Drug Discovery
    • 18th, Cambridge, MA, speakers from: AbbVie, AstraZeneca, Cresset, Elixir Software, Intellegens, Novartis, Optibrium, Takeda
    • 23rd, San Diego, CA, speakers from: Cresset, Elixir Software, Intellegens, Lilly, Optibrium, Retrophin, Takeda
    • 25th, San Francisco, CA, speakers from: Cresset, Elixir Software, Intellegens, Lilly, Novartis, Optibrium

See all events.