June 2018 newsletter

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.


Upcoming events

  • 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.

Presentations from the Cresset User Group Meeting 2018

Thank you to all attendees who contributed to the success of the Cresset User Group Meeting 2018. We are grateful to the speakers and exhibitors for permission to share the presentations below.

We hope to see you at the Cresset User Group Meeting 2019 on 19-20 June in Cambridge, UK.


Cresset User Group Meeting 2018 invited speakers and meeting chairman, left to right: Rob Scoffin, Cresset; Jun Xu, Sun Yat-sen University; Stevan W Djuric, AbbVie, Antonia Mey, University of Edinburgh; Richard Lewis, Novartis; Graeme Stevenson, Cancer Therapeutics CTX; Kazuyoshi Ikeda, Keio University; Ashraf Zarkan, University of Cambridge.

 


Cresset User Group Meeting 2018 scientific program delegates.

 


3 of the 12 workshops at the Cresset User Group Meeting 2018.

“One of the best meetings I’ve ever been to. Good science. Collaborative and engaging discussions in a wonderful atmosphere.”

Flare™ V2 heralds next generation of structure-based design with Electrostatic Complementarity™ scoring and new Python® API

Cambridge, UK – 20 June 2018 – Cresset, innovative provider of software for molecular discovery, is pleased to announce the release of Flare V2. Introducing major enhancements to ligand design and activity prediction in a modern, extensible, scriptable interface, Flare V2 raises the bar in structure-based design.

Make rapid activity predictions using Electrostatic Complementarity™

“Our commitment to innovation sees the introduction of Electrostatic Complementarity (EC) to Flare. This ground-breaking new technique promises a radical change in new molecule design,” says Dr Mark Mackey, CSO at Cresset.

EC scores and maps provide rapid activity prediction with visual feedback on new molecule designs. Chemists will better understand ligand binding, structure-activity relationships and the ranking of new molecule designs. Based on Cresset’s polarizable XED force field, the EC calculation is fast and predictive.

New Python® API makes Flare massively extensible

“The new Python® API enables chemists to create their own workflows and automate common tasks making Flare easy to customize and extend,” says Dr Tim Cheeseright, Director of Products at Cresset.

The Python API gives full access to all of Flare’s capabilities, including the RDKit cheminformatics toolkit, plus Python modules for graphing, statistics, Jupyter® notebook integration and other features.

Major enhancements to workflow and usability

Flare V2 includes over 200 new and improved features covering usability, multi-parameter scoring, ensemble docking and more.

Computational, medicinal and synthetic chemists are encouraged to request a free evaluation of Flare.

Flare V2 makes advanced structure-based design techniques, such as Electrostatic Complementarity, multiparametric scoring and Python scripting, accessible through an intuitive GUI.

The healing potential of tango for people living with Parkinson’s: Upcoming events

Cambridge, UK – 14 June 2018 – Cresset, innovative provider of outstanding software for molecular discovery, is pleased to announce its support for ‘Parkinson’s and the Tango Effect’, a book written by Kate Swindlehurst, a tango dancer living with a diagnosis of Parkinson’s. It is being crowd-funded through the publisher Unbound.

‘Parkinson’s and the Tango Effect’ began with a tango lesson and grew into an exploration of the healing potential of tango. The book builds on research on the impact of dance on Parkinson’s symptoms and takes it a stage further, with a behind-the-scenes record of private lessons and contributions from tango teachers. It documents the emotional and social benefits of the dance and its impact on the quality of life for people living with Parkinson’s.

Kate will be talking about the book and her experiences in three upcoming events:

May 2018 newsletter

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.

Upcoming events

  • 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.

Cresset User Group Meeting 2018 to showcase new science, customer case studies and hands-on software workshops

Helping chemistry teams design the best molecules

Cambridge, UK – 15 May 2018 – Cresset, innovative provider of outstanding software for molecular discovery, is pleased to announce the scientific program for its User Group Meeting on 21st – 22nd June in Cambridge, UK.

“Leading chemists from industry and academia will present scientific case studies and insights into how computational chemistry has helped transform their research,” says Dr Robert Scoffin, Cresset CEO. “In addition, Cresset scientists will present our latest scientific developments and will showcase upcoming applications to help chemistry teams 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, we invite you to join us.”

Registration is open to computational, medicinal and synthetic chemists, and those wanting to design the best molecules efficiently.

June 21 • Scientific program

Cresset presentations:

  • Sneak Peek at Next Generation Collaborative 3D Design
  • Real Time 3D Design in 2D!
  • Customizing and Scripting in Flare 2.0: Introducing the New API
  • Predicting Activity Using the Electrostatic Complementarity TM of Protein-ligand Complexes
  • New Science and Improved Workflows in Cresset Ligand-based Applications

Invited presentations:

  • Keynote lecture: Acceleration of Drug Discovery Through the Judicious Application of Enabling Chemistry Technology, AbbVie, USA
  • Molecules in 5D: Experiences with Peptidic Macrocycles, Novartis, Switzerland
  • Indole Regulation of Cytoplasmic pH makes E. coli More Resilient to Antibiotic Stress, University of Cambridge, UK
  • Exploring the Potential of Indirect Inhibition of GTPase Driven Oncogenesis via ICMT Inhibition, Cancer Therapeutics CRC, Australia
  • Identifying Pharmaceutical Molecules with a Chemotyping Approach, Sun Yat-sen University China
  • Progress of Compound Library Design Using In-silico Approach for Collaborative Drug Discovery, Keio University, Japan
  • Pushing the Boundaries of Computational Binding Free Energy Prediction Methods, University of Edinburgh, UK

 June 22 • Hands-on software workshops

  • Introduction to Flare for computational, medicinal and synthetic chemists
  • Python in Flare
  • Advanced Spark
  • 3D-QSAR in Forge
  • Forge SAR
  • Library design with Cresset nodes in KNIME

END

 

April 2018 newsletter

A sneak peek into Flare V2: Python API and new science

As promised, Flare V2, due for release next month. Giovanna Tedesco gives a sneak peek into the new Flare Python API, new science and significant improvements to functionality and usability.


In the Cresset lab: Molecular design re-imagined

Tim Cheeseright describes how project TorchWeb will enable medicinal chemists to make the best, most informed decision at every stage of the discovery process.


The Cresset User Group Meeting, Cambridge, UK

June 21 • Scientific program

  • AbbVie, Novartis and UCB will be presenting in our strongest ever scientific program
  • Cresset scientists will present for the first time our new approach to rapid activity prediction, introduce our web based collaboration platform for new molecule design and showcase updates to our ligand-based applications.

June 22 • Hands-on software workshops – spaces filling fast

  • Introduction to Flare
  • Python in Flare
  • Advanced Spark
  • 3D-QSAR in Forge
  • Forge SAR
  • Library design with Cresset nodes in KNIME

If you require accommodation on-site please book soon as there is limited availability left.

Find out more and register.


Pharmacophore constraints – when should they be used?

New pharmacophore constraints developed by Cresset are useful for more than just virtual screening. Mark Mackey explains how, and the effect adding constraints has on the probability of a successful ligand alignment.


Flexible academic licensing

Academic customers tell us that our applications help them communicate ideas, give new insight, and are easy to learn and use. See the flexible licensing options available to academics.


Review of the CCPBioSim training week

Matthias Bauer reviews the Collaborative Computational Project for Biomolecular Simulation (CCPBioSim) training week hosted by the University of Bristol.


Recent citations

  • Computer-aided drug design, synthesis and identification of disulfide compounds as novel and potential allosteric PAK1 inhibitors, RSC Adv., 2018,8, 11894-11901.
  • Activity and selectivity cliffs for DPP‐IV inhibitors: Lessons we can learn from SAR studies and their application to virtual screening, Medicinal Research Reviews

See these and other citations.


Upcoming events

  • 26 April, 29th Symposium on Medicinal Chemistry in Eastern England, Hatfield, UK
  • 29 April – 2 May, 36th National Medicinal Chemistry Symposium, Nashville, TN, USA
  • 4 May, NESACS: 7th Advances in Chemical Structures, Cambridge, MA, USA
  • 14 May, Kinase 2018, Cambridge, UK
  • 14 – 18 May, Workshop on Free Energy Methods, Kinetics and Markov State Models in Drug Design, Boston, MA, USA
  • 27 – 31 May, 11th International Conference on Chemical Structures, Noordwijkerhout, The Netherlands

See all events.


Compliance with the General Data Protection Regulation

We have always complied with data protection and have recently updated our privacy policy in accordance with the General Data Protection Regulation (GDPR) that comes into effect on May 25, 2018. Cresset has been sending newsletters every month for at least the last 6 years and we have always given the opportunity to opt-out. As you have not previously opted-out you continue to receive this newsletter under GDPR Legitimate Interest. You will always have the opportunity to opt-out at any time.

Flexible academic licensing

Are you a:

  • PhD student or postdoctoral researcher
  • Course tutor
  • Principal investigator
  • Department head?

Did you know that:

  • You can access Cresset ligand-based desktop applications through a variety of flexible licensing options
  • If you publish work which used Cresset technology, and you cite the applications used, we will promote your work through our website and newsletter?

Apply Cresset to your research

Academic customers tell us that our applications help them communicate ideas, give new insight, and are easy to learn and use. Below are just a few examples of how you can apply Cresset technology to your research.

Active design using electrostatics

Torch’s ligand-centric view enables 3D design whether or not you have a protein crystal structure. It makes it easy for you to focus on the designs that work and have good physicochemical properties.

Electrostatic and shape descriptors provide a rich informed view to help you understand the effects of chemical changes and eliminate designs that are unlikely to be active.


Figure 1: A change on one side of the molecule can often influence a distal region, especially if the systems are electronically linked through π-systems. This simple change has multiple effects due to the increased electron-withdrawing character of the new heteroatom and the addition of an aromatic ring: (A) the boundary of negative electrostatic potential extends further; (B) the shape and size of the negative π-cloud is significantly altered; (C) the size and extents of the positively charged aromatic edge are increased; and (D) there is a small increase in the positive potential associated with the aromatic hydrogens of the pyrimidine nucleus at the other end of the molecule.

Find and understand activity and selectivity cliffs in your SAR

Activity Miner, a component of Torch and Forge, helps you find and understand critical regions in complex SAR. Using the concepts of activity cliffs and matched molecular pairs, you can link activity changes to electrostatic and shape changes. Since selectivity is often as important as activity, Activity Miner makes it easy for you to compare multiple end points. The design process in Torch enables you to apply this knowledge to progress your project.

Activity Miner top pairs
Figure 2: Pinpoint the most significant changes to your molecules using the sortable top pairs table. Find critical points in the SAR and understand how they relate to changes in physicochemical properties.

Powerful models to interpret your data

Forge uses the Cresset patented ligand alignment algorithm to generate realistic, interpretable relationships between your molecules. It includes an impressive range of SAR models that combine robust analysis with customizable parameters, ease of use and intuitive visualization. For SAR analysis, there is no need to look any further than Forge.


Figure 3: QSAR models in Forge decipher complex SAR and inform the design of new molecules.

New SAR insights form novel methods


Figure 4: Activity Atlas is a novel, qualitative method that generates three distinct maps of the electrostatic, shape and hydrophobic properties around your molecules. It can be used with small or large data sets and is particularly useful for projects where traditional 3D-QSAR approaches fail.

Find biologically equivalent alternatives to escape IP and toxicity traps

Customers tell us that Spark is the best scaffold hopping and bioisostere replacement tool they have ever used. The easy to use interface quickly generates a range of novel molecules from an initial structure. Profiling and scoring help you choose the most innovative and tractable leads with the properties you need.


Figure 5: Spark workflow.

Request an academic license

Testimonials

Molecular visualization makes it easier to communicate ideas

“Working with Cresset tools has helped me generate new ideas for my projects in various disease areas. The molecular visualization has made it easier to communicate my ideas to my experimental collaborators, both chemists and biologists.”

New insight

“Cresset’s software gives new insight to projects I’ve been working on for the past three to four years. I specifically use it to see how proteins, DNA and molecules interact and bind to each other. If we can design drug molecules that will bind to DNA the same way proteins do, we can open up whole new lines of therapy. Cresset is supportive of academic research and they’ve been wonderful to work with to get everything up and running.”

Easy to learn and use

“Our students who use the Cresset systems in their projects tend to gain an affinity with a number of med-chem concepts far earlier than those who do strictly organic projects, for example using Spark to identify new frameworks that possess favorable properties and which can then be synthesized in the lab via a novel reaction. Compounds can be tracked within a TorchLite template and the student can invoke field patterns and orbital coefficients to explain changes to NMR spectra.”

 “My students and I are very grateful for providing us with the educational license and thus an opportunity to explore Cresset’s software in our lectures. Cresset provides marvelous software, easy to learn, easy to use, pleasant looking and its structure is logical and educational. The program manuals are great.”

 “Considering the absence of an experimental structure, the field based concept was a perfect match for our work. It helped us obtain bioactive conformations of ligands based on a validated pharmacophore. The software provided by Cresset is user easy and user friendly, creative and flexible for a new starter to an experienced researcher to use.”

“Visualizing the inhibitor/substrate binding site of protein crystal structure in Cresset using field points calculated by XED force field is very informative. The protocols for all the modules in Cresset are very quick and easy to use. Forge and Spark are excellent programs for LBDD. The radial plots obtained from alignment methods implemented in Forge provide a visual inspection of results and could be effectively used for simultaneously comparing any number of physical properties for the compounds in the dataset. I strongly believe that Cresset software is an important inclusion in the spectrum of software programs used for Computer Aided Drug Discovery paradigm.”

 

March 2018 newsletter

Flare: Accessible structure-based design

Tim Cheeseright, Director of Products, describes how a balance of usability and flexibility, with a focus on design and accessible methods, have contributed to accessible structure-based design with Flare™.


New Spark databases released

The release of Spark™ V10.5 in February brought completely new Spark databases. Derived from molecules in ZINC, eMolecules’ Screening Compounds and ChEMBL 23, they include over 3 million unique entities.


Full speaker line-up announced for The Cresset User Group Meeting

With speakers representing 7 countries across 4 continents, the scientific program for The Cresset User Group Meeting will give attendees insight to the use of computational chemistry in industry and academia.


Recent presentation, poster and citations

See all citations.


Review of 255th American Chemical Society Meeting

Martin Slater, Director of Consulting Services, reviews his first experience of ACS. From fragrances, food and cheminformatics to GPCRs it proved to be both exhilarating and enlightening.


Upcoming events

  • April 2-6: Drug Discovery Chemistry, San Diego, CA, USA Meet us on stand 502 and see our poster: Deciphering Kinase SAR using Electrostatics
  • April 5: Applied Pharmaceutical Chemistry, Boston, MA, USA See our poster: Deciphering Kinase SAR using Electrostatics
  • April 9-13: CCPBioSim Training Week, Bristol, UK We are proud to be supporting CCPBioSim is their drive to improve and integrate biomolecular simulation software
  • April 11-12: UK QSAR and MGMS Structure-Activity Relationships, Cardiff, UK Meet us on stand 5 in the exhibit hall
  • April 26: 29th Symposium on Medicinal Chemistry in Eastern England, Hatfield, UK See our poster: Deciphering Kinase SAR using Electrostatics
  • April 29: 36th National Medicinal Chemistry Symposium, Nashville, TN, USA Meet us in the exhibit hall

See all events.


Cresset Commercial Director to run 19th marathon

On April 29, David Bardsley will run his 19th marathon in Newport, Wales, UK. David is fundraising for DEBRA, a charity that supports individuals and families affected by Epidermolysis Bullosa – a painful genetic skin blistering condition.

Parkinson’s UK, Selcia, and Cresset collaborate to discover new drug candidates for Parkinson’s

London, Ongar and Cambridge, UK – 8 March 2018 – A new collaboration in the efforts to find a new drug candidate to combat Parkinson’s has been announced in the UK today.

The collaboration, formed by leading charity Parkinson’s UK, contract innovation and research organization, Selcia (part of Eurofins), and computational chemistry software and services provider, Cresset Discovery Services, is centred on creating novel molecules that could stop or slow the progression of the condition.

By modulating gene transcription, the collaboration aims to create molecules that increase the activity of a selection of genes which have the potential to both increase dopamine synthesis to ease symptoms, and boost the production of proteins which have neuroprotective effects. Parkinson’s UK is set to fund the £1.2million project, which will take place over 12 months.

This collaboration represents an expansion of Parkinson’s UK’s Virtual Biotech programme of work, which allows the charity to provide leadership and critical funding to early drug development in partnership with a range of other organisations that have the facilities and staff to carry out scientific work on a contract basis.

Dr Arthur Roach, Director of Research at Parkinson’s UK, said: “It’s fantastic to be working in partnership with these organisations, which have an exceptional range of skill and expertise in drug discovery. We’re also very excited to be working to identify a novel candidate that will not only be dopaminergic but also neuroprotective. Should initial studies go well, we could be looking at a new drug that has the potential to help millions of people with Parkinson’s across the world.”

Dr Vicky Steadman, Director of Discovery at Selcia, commented: “We are delighted that our proposal to Parkinson’s UK translated into the initiation of a collaboration that could lead to novel treatments for people with Parkinson’s. Selcia has an enviable track record in delivering pre-clinical candidates from lead optimization projects, and considerable expertise in designing drug candidates that cross the blood-brain barrier.”

Dr Martin Slater, Director, Cresset Discovery Services, said: “The combined strengths of the collaborating partners enables us to efficiently address the very difficult challenge of finding new medicines for this neurodegenerative condition. Cresset Discovery Services will provide unique cutting edge molecular modelling capability, our extensive AI capabilities and in silico expertise, to aid in the discovery of the most appropriate starting points for this program.”

ENDS

For further information, contact:

Parkinson’s UK: Kirsty Callingham, Senior Media and PR Officer, kcallingham@parkinsons.org.uk +442079 639311

Cresset: Sue Peffer, Marketing Manager, news@cresset-group.com, +44 1223 858890.

Selcia: Vicky Steadman, Director, Discovery Vicky.steadman@selcia.com 01277 367042.

About the partners

Parkinson’s UK

Parkinson’s UK is the UK’s leading charity supporting those with the condition. Its mission is to find a cure and improve life for everyone affected by Parkinson’s through cutting edge research, information, support and campaigning. For more information, visit www.parkinsons.org.uk

Selcia Ltd

Selcia Ltd is a UK-based provider of integrated drug discovery services with a worldwide client base. Founded in 2001, its workforce comprises industry experienced medicinal chemists, biologists and ADME scientists as well as 14C radiolabeling experts. Selcia announced its acquisition by Eurofins earlier this year.

Cresset Discovery Services

Cresset Discovery Services manages and delivers outsourced computational chemistry programs. Experienced scientists work alongside your chemists to solve problems, provide fresh ideas, remove roadblocks and add direction and insight. Cresset Discovery Services helps their customers reach their milestones faster and more cost effectively. For more information, please visit www.cresset-group.com/discovery-services

Eurofins

Eurofins – a global leader in bio-analysis believes it is the world leader in food, environment and pharmaceutical products testing and that it is also one of the global independent market leaders in certain testing and laboratory services for agroscience, genomics and discovery pharmacology and for supporting clinical studies. In addition, Eurofins is one of the significant emerging players in specialty clinical diagnostic testing in Europe and the USA.

As one of the most innovative and quality oriented international players in its industry, Eurofins is ideally positioned to support its clients’ increasingly stringent quality and safety standards and the expanding demands of regulatory authorities and healthcare practitioners around the world.

The shares of Eurofins Scientific are listed on the Euronext Paris Stock Exchange (ISIN FR0000038259, Reuters EUFI.PA, Bloomberg ERF FP).