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 ….
- All Flare functionality can be accessed from the command line: see Gitlab for more information.
- 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.•
- 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.
- 2-3, OpenTox Asia, Hyderabad, India
- 20-23, 139th Annual Meeting of the Pharmaceutical Society of Japan, Chiba, Japan
- 24-26, 7th RSC-BMCS Fragment-based Drug Discovery, Cambridge, UK
- 31-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
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
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.
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
- 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.
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.
- 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.
- 31 October-2 November, AusBiotech 2018, Brisbane, Australia
- 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
See all events.
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.
- 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.
- 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.
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.
- 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.
- 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
- 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.
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 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.
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.
Flare V2 released: New science and functionality
Giovanna Tedesco introduces the new science and functionality in Flare V2, including: Electrostatic ComplementarityTM, enhanced protein surface coloring, ensemble docking, enhanced ligand-design functionality, Python API.
Flare API: A new playground for computational chemists and developers
The Python API in Flare enables both high-level access to scientific functionality with the aim to automate tasks, and low-level access to the graphical user interface and internal processes, thus enabling the implementation of own algorithms and customization of the interfaces through addition of user-defined controls. Paolo Tosco describes the different ways to deal with Python code in Flare, ranging from plain execution of Python scripts through the interpreter to the highly interactive Jupyter QtConsole and Notebooks.
Review of 11th International Conference on Chemical Structures
Paolo Tosco captures the highlights of talks he found most inspiring at the 11th International Conference on Chemical Structures, even though the list could indeed be much longer.
Presentations from the Cresset User Group Meeting
The excellent feedback from delegates who attended the Cresset User Group Meeting last week reflect our own view that this was an excellent forum for great science and collaborative discussion in a wonderful atmosphere. Thanks are extended to the speakers and exhibitors who contributed to the meeting and who have given permission for us to share their presentations.
Date for your diary: Cresset User Group Meeting 2019 on 19-20 June, Cambridge, UK.
- 4-6 July: RICT, Strasbourg, France
- Meet us at booth 25
- See our poster: Rapid and Accessible In-silico Macrocycle Design: Application to BRD4
- 19-23 August: 256th ACS National Meeting
- 19th August:
- MEDI poster: Rapid and Accessible In-silico Macrocycle Design: Application to BRD4
- 21st August:
- COMP oral: Rapid and Accessible In-silico Macrocycle Design
- COMP poster: Deciphering Kinase SAR Using Electrostatics
See all events.
Last chance to register for Cresset User Group Meeting, 21-22 June
With just four weeks until the Cresset User Group Meeting scientific program, we encourage you to secure your registration no later than 6th June.
- Scientific program, June 21: Stevan W Djuric, AbbVie will deliver the keynote lecture, with additional invited presentations from Novartis, Cancer Therapeutics CRC, University of Cambridge, Sun Yat-sen University, Keio University, University of Edinburgh, and Cresset will present latest science and showcase upcoming applications.
- Workshops, June 22: Very limited spaces remain on these hands-on software workshops: Introduction to Flare, Python in Flare, Advanced Spark, 3D-QSAR in Forge, Forge SAR, and Library design with Cresset nodes in KNIME.
A sneak peek into Flare V2: A major advancement for structure-based design with Flare
Flare V2 is in the final rounds of testing, which means the release announcement is imminent. Ahead of the user group meeting, where we will be presenting this major advancement, this post takes a sneak peek at some of the new features in this version.
Review of 8th RSC/SCI symposium on kinase inhibitor design
Martin Slater’s review of Kinase 2018 focuses on talks discussing lipid kinases, kinase activators and kinase inhibitors for the CNS.
- 4-7 June, BIO International 2018, Boston, MA, USA
- 7-8 June, 19th Annual Drug Discovery Summit, Berlin, Germany
- 7-8 June, New Frontiers in Ocular Therapeutics 2nd Edition, Dublin, Ireland
- Mark Mackey, CSO, presenting on ‘In silico virtual screening to provide new candidates for drug discovery’
- 7-10 June, 2nd Worldwide Chinese Computational Biology and Molecular Simulation Conference, Guangzhou, China
- 21-22 June, Cresset User Group Meeting 2018, Cambridge, UK
See all events.
Parkinson’s and the Tango Effect
Through our corporate social responsibility, we are delighted to support Kate Swindlehurst who is promoting the healing potential of dance for those with Parkinson’s.