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.


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.

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.

July 2018 newsletter

Launch of Cresset Python extensions for Flare

Python scripts that extend the functionality of FlareTM, our structure-based design platform, are now available for download from GitLab. This includes scripts written by Cresset that extend the functionality of Flare, scripts that use pyflare to create command line workflows and example scripts for developers.


Flare V2 keyboard shortcuts

See at a glance the keyboard shortcuts for V2 of Flare and the Flare Molecule Editor.


Spark reagent databases

Access the latest information on reagent availability to refine your SparkTM results. Download the updated version of the Spark reagent databases, based on the eMolecules Building Blocks collection.


We’re hiring!

We’re recruiting for a European Application Scientist, based in the UK. The successful applicant will provide scientific support to our existing customer base and commercial team.


Symposium on Streamlining Drug Discovery

These one day symposia, delivered by Cresset, Optibrium and Elixir, will highlight new approaches and technologies being applied to the search for future therapeutics.

Free to attend, these events are aimed at scientists from pharmaceutical, biotechnology, agrochemical, flavor and fragrance organizations, not-for-profits and academia who wish to get a broad appreciation of the latest advances in drug discovery delivered by key scientists and thought leaders from leading organizations.


Upcoming events

August 19-23: 256th ACS National Meeting, USA

August 19: MEDI poster: Rapid and Accessible In-silico Macrocycle Design: Application to BRD4

August 21: COMP oral: Rapid and Accessible In-silico Macrocycle Design; COMP poster: Deciphering Kinase SAR Using Electrostatics

September 2-6: XXV EFMC International Symposium on Medicinal Chemistry, Slovenia

  • Meet us on stand 32 and see our poster ‘Rapid and Accessible In-silico Macrocycle Design – application to BRD4′

See all events.