April 2017 newsletter

Last chance for early access to Flare, new structure-based design application

Contact your account manager to join the final round of Flare testing and gain early access to this cutting edge structure-based design method with intuitive GUI.

The Cresset User Group Meeting

June 29th, Scientific program

  • Official launch of Flare, our new structure-based design application
  • Update on science and ligand-based design applications
  • Invited speakers from 4 continents share their use of Cresset applications on topics including fragment screening, library design, protein-ligand binding, virtual screening and fragrance molecule design.

June 30th, Hands-on software workshops

Due to demand which meant some workshops were fully booked, we have now created additional spaces. If the workshop you were interested in was fully booked then check back to see if space is now available.

Hit to lead

A long-standing customer had a hit series with good activity but poor properties. See how Cresset Discovery Services worked closely with the customer to formulate a plan of action to optimize the compound properties while maintaining potency.

Recent citations

See the following new citations:

  • Discovery of Compounds that Positively Modulate the High Affinity Choline Transporter
  • Chemical composition and phagocyte immunomodulatory activity of Ferula iliensis essential oils
  • Structure-Based Library Design and Fragment Screening for the Identification of Reversible Complement Factor D Protease Inhibitors
  • Field Based 3D-QSAR Model of KATP Channel Activation by 4, 6 Di-substituted Benzopyran Derivatives

Presentations from ACS

Download our presentation and posters from the 253rd ACS National Meeting. Also available are the presentation and poster by the University of Bristol which feature Flare, our new structure-based design application.

Presentations and posters from 253rd American Chemical Society National Meeting

Download our presentation and posters from the 253rd ACS National Meeting. Also available is the presentation, and poster, by the University of Bristol which features Flare, our new structure-based design application.

Improving new molecule design using electrostatics

MEDI poster 135

Tim Cheeseright, Director of Products, Cresset

Electrostatics are critical to ligand binding and yet largely overlooked in new molecule design due to the difficulty in calculation and visualization of meaningful potentials. We have previously shown how electrostatics can be used effectively for scaffold hopping, virtual screening, ligand alignment and SAR interpretation. In this poster we will focus on ligand and protein electrostatics. We will show how considering the changes in ligand electrostatics improves the outcome for new molecule design. Going beyond traditional H-bonding based pharmacophore descriptors enables designers to map the effect of molecular changes on the full electrostatic potential of their molecules. Full exploitation of aromatic dipole moments, C-H hydrogen bonding, halogen bonds, and pi-pi interactions is only possible by understanding the electrostatic basis of these effects. Consideration of the protein electrostatics can inform ligand design to generate complementary patterns of electron rich and electron poor regions.

Putting electrostatics and water at the center of structure-based drug design

COMP poster 292

Tim Cheeseright, Director of Products, Cresset

The electrostatics of protein active sites can inform ligand design and SAR. However, no calculation of electrostatic potentials in the active site can be complete without also considering whether water molecules are tightly bound and contributing to the potentials and ligand binding. In this poster we will explore the effect of including water molecules shown to be energetically favorable on the electrostatic potential of individual proteins. We will present a new application to enable rapid and accurate calculation of water stability and protein interaction potentials. Combining these analyses with the popular Waterswap technique results in an in-depth knowledge of protein targets and ligand protein binding.

Combining protein interaction potentials with water analysis in structure-based design

COMP oral 497

Tim Cheeseright, Director of Products, Cresset

The XED molecular mechanics force field is unique in providing off-atom centered charges that enable studying complex charge distributions in ligands and proteins alike. We have previously described the use of the molecular interaction potentials derived from the XED force field for ligand similarity calculations which have, in turn, enabled virtual screening, scaffold hopping and SAR analysis to be performed using these effective and meaningful descriptors. In this talk we will describe in detail our application of the XED force field to proteins. We will focus on the calculation of protein interaction potentials showing how protein electrostatics provide deep insights into ligand binding that would otherwise be missed. In parallel to the calculation of the protein interaction potentials we describe using XED to minimize protein-ligand complexes and demonstrate the synergy between these methods.

Understanding protein-ligand binding at the molecular level: Using swap-based methods to visualise binding free energy components

COMP oral 103

Christopher Woods, University of Bristol

Binding free energy methods allow computational chemists to predict whether or not changes to a ligand increase or decrease its binding affinity to a medicinally important protein. While these methods can reveal whether or not a change to the ligand increases its binding affinity, they provide little information as to how this change affects individual molecular interactions. Such information would be extremely useful, as it could provide feedback to a drug designer that could inspire the next series of ligand modifications. For example, it would be valuable for the free energy calculation to reveal that addition of a hydroxyl group to a ligand strengthens its interaction with an active site aspartate residue, but simultaneously destabilises a water molecule that bridges between it and the protein. This feedback could inspire a drug designer to investigate ligand modifications that combine addition of the hydroxyl group with the addition of moeities that displace the bridging water molecule. We have developed a range of binding free energy methods, based on WaterSwap. These swap-based methods allow calculation of absolute and relative protein-ligand binding free energies using a single simulation over a single λ-coordinate. Use of a single coordinate allows components of the binding free energy (i.e. specific interactions between the ligand and individual active-site residues, or between the ligand and neighbouring water molecules) to be integrated across λ during the simulation. The resulting components are used to colour-code 3D views of the proteinligand system. This allows drug designers to easily visualise the affect of ligand modifications on the interactions between the ligand and individual residues in the protein, and individual water molecules in the binding site. These components are not true free energies. However, what they reveal is chemically intuitive, and provide a level of insight that allows drug designers to suggest modifications that lead to improved binding affinity. The components show cooperative affects, and also reveal how increasing the strength of interaction

Visualising the molecular drivers behind drug resistance

COMP Sci-Mix poster 347

Christopher Woods, University of Bristol

The huge expense of developing a new drug can be wasted if natural mutations of amino acid residues in the targetted protein lead to a loss of drug binding affinity. Rational drug design is a continual struggle, with evolution driving mutations that develop emerging drug resistance into widespread drug inefficacy. We have developed a new free energy method, based on WaterSwap, that can provide drug designers with the insight needed to understand how protein mutations affect drug binding. This method allows the change in binding free energy of the drug associated with the mutation of the protein to be predicted. In addition, as for other Swap-Based methods, this free energy change can be decomposed into components that can be used for visualisation. These components allow the change in binding free energy to be understood in terms of changes in specific ligand-protein interactions, or changes in the solvating water network in the active site. This method allows drug designers to pro-actively screen a new drug computationally against a range of likely protein mutants, thereby enabling the drug designer to get one step ahead of nature. Alternatively, it allows drug designers to investigate the molecular basis for reduced binding affinity in known drug-resistant mutants of a protein. This information would be useful for the development of the subsequent generations of the drug.

March 2017 newsletter

Flare sneak peek

Take a sneak peek at Flare, our new structure-based design application. See how the innovative features and new science combine to give you new insights into structure-based design.

Blaze used in discovery of allosteric modulators of the high affinity choline transporter

Scientists from Pfizer, Neusentis, Nanion, and Kissei have identified 9 new active small molecules that modulate the pathway of interest. 5 of these were identified from the Pfizer corporate compound library using a set of 887 compounds chosen using Cresset’s Blaze virtual screening software.

Cresset signs strategic alliance agreement to speed up drug design

Our collaboration with the school of Pharmaceutical Sciences, Sun Yat-Sen University, and iPrecision Medicine Technology Inc., brings together expertise and innovation in development technologies for computational molecule design.

Spark reagent databases

Get the very best availability information on which reagents to order. Download the March release of the Spark reagent databases using the Spark Database update widget (instructions on the installing Spark databases page), or contact us if you would like to use a command line utility (such as wget).

Tips and tricks

  • Setting up a FieldTemplater experiment
  • Merging structure and activity files
  • Rigid-body ligand alignment
  • See all tips and tricks.

Meet us in April

  • April 1st: COMP Saturday Social with CINF, CA, USA co-sponsored by Cresset
  • April 2nd – 6th: ACS, San Francisco, CA, USA. Cresset applications will feature in the following oral/poster presentations:
    • Improving new molecule design using electrostatics
    • Putting electrostatics and water at the center of structure-based drug design
    • Combining protein interaction potentials with water analysis in structure-based design
    • Understanding protein-ligand binding at the molecular level: Using swap-based methods to visualise binding free energy components
    • Visualising the molecular drivers behind drug resistance
  • April 24th – 27th: Drug Discovery Chemistry, San Diego, CA, USA
    • Meet David Bardsley at booth 404 for a preview of Flare, our new structure-based design application

Have you registered for The Cresset User Group Meeting?

June 29th, Scientific program

Join us to hear speakers from 4 continents share their use of Cresset applications on topics including fragment library design, protein-ligand binding, virtual screening and fragrance molecule design. We will showcase Flare, our exciting new structure-based design application, give an update on our ligand-based tools and a peek into the heart of new Cresset science.

June 30th, Hands-on software workshops

  • Introduction to Flare for computational, medicinal and synthetic chemists
  • SAR with Forge
  • Spark: Introduction and advanced
  • Virtual screening with Cresset
  • 3D-QSAR
  • Torch

Find out more and register.

Cresset signs strategic alliance agreement to speed up drug design

Cambridge, UK – 28 March 2017 – Cresset, innovative provider of software and contract research services for small molecule discovery and design, signs three-way strategic agreement to speed up drug design.

Dr David Bardsley, Commercial Director, Cresset visited the School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China to sign a strategic cooperation agreement for drug design technology, developed within the Research Centre for Drug Discovery (RCDD). This visit was in response to an invitation from Professor Jun Xu, RCDD, and was hosted by Mr Wenhao Hu, Dean of the School, and Huichang Bi, Vice Dean of the School for International Development.

A further agreement was signed between Dr Bardsley and Mr DeKang Zhang, Chairman, iPrecison Medicine Technology Inc., whereby Cresset will promote iPrecision software and technology globally. This agreement follows the transfer of 10 drug design software patents from RCDD to iPrecision last year.

“This British-Chinese three-way agreement brings together expertise and innovation in development of technologies for computational molecule design”, says Dr Bardsley, Cresset. “I look forward to working with each organization to establish global distribution channels.”

Back row, left to right: Huichang Bi, Professor Jun Xu, DeKang Zhang, Zhishu Huang

Front row: left to right: Mr Wenhao Hu, Dr David Bardsley

Left to right: Huichang Bi, Dr David Bardsley, Mr Wenhao Hu, DeKang Zhang, Professor Jun Xu, Zhishu Huang

 

February 2017 newsletter

Case study: Conduct ligand-protein docking

Find out how we conducted ligand-protein docking to narrow down a 50k compound library to the best 1.5k compounds at a fraction of the cost of buying and screening the entire 50k library.


RDKit molecular simulations through OpenMM

Paolo Tosco describes how RDKit is used in Cresset software and presents preliminary work on boosting RDKit molecular simulations through OpenMM.
 
 


Web clip tips and tricks

  • Changing preferred alignments
  • Importing pre-existing conformations
  • Using Tags to organize data sets

See more tips and tricks.


Flexible licensing terms for academics

Cresset support the academic community through flexible licensing terms. Licenses have been created specifically to facilitate academic research and teaching within a university.


Cresset User Group Meeting, 29-30 June – workshop spaces limited

The day after the scientific program we will hold hands-on software workshops – spaces are limited so early registration is encouraged.

January 2017 newsletter

New visual identity for Cresset

Today we unveil our new visual identity. This reflects a new structure for our growing business and the different markets we serve: Cresset software, Cresset Discovery Services and Re-Pharm.


Call for beta testers for Flare, our new structure-based design application

Flare provides new insights for structure-based design by integrating cutting edge approaches from Cresset with significant open source and commercial methods. Flare will be available for beta testing in early February.


Case studies from Cresset Discovery Services

Outsourced computational chemistry projects come with an incredibly varied range of scope and focus. These case studies give an idea of the breadth and flexibility of our customer projects.


Registration open for Cresset User Group Meeting, 29-30 June

Scientific program features an excellent line-up of speakers from 4 continents – each of who we are delighted will present in person. Hands-on software workshops exploring Cresset applications for computational, medicinal and synthetic chemists.
Find out more and register.

Cresset corporate rebrand reflects new structure for growing company

Cambridge, UK – 25 January 2017 – Cresset, innovative provider of software and contract research services for small molecule discovery and design, is pleased to announce a corporate rebrand, reflecting a new structure for this growing business.

“Cresset has grown dramatically since I joined as CEO in 2010, with a tripling of annual income over this period” says Dr Robert Scoffin, CEO of Cresset. “This new visual identity formalizes our structure into three divisions, reflecting the markets we serve and creating the conditions for even greater future growth.”

Cresset software: innovative science • intuitive software

The world’s leading research organizations use Cresset software on a daily basis to solve challenges in small molecule discovery, design and optimization.

“Our innovative science is delivered in a range of intuitive software for computational and medicinal chemists,” says Dr Tim Cheeseright, Director of Products. “Our passion for the continual development of the Cresset science and technology is reflected in the loyalty of our customers and strong business growth. Our software delivers results that our customers rely on.”

Cresset Discovery Services: make the molecules that matter

Cresset Discovery Services manages and delivers fully integrated outsourced computational chemistry programs from early to late stage discovery. In the last decade they have delivered hundreds of projects to customers ranging from small biotechs to pharmaceutical giants.

“We help chemists to understand as much as possible about the systems they are working on,” explains Dr David Bardsley, Commercial Director. “This enables our customers to save time and money by directing their scientific resources in the direction most likely to succeed and towards the molecules that matter.”

Re-Pharm: smarter drug re-profiling

Re-Pharm combines expert scientific insight with proven computational technology to identify and progress existing compounds that are suitable candidates for re-profiling against new disease indications.

“Re-Pharm demonstrates the power of Cresset software for rapidly identifying compounds, such as RP0217, that are likely to be active against disease targets.” says Dr Robert Scoffin, CEO of Re-Pharm and Cresset. “We have been granted patents on and are currently licensing  RP0217 for respiratory and ophthalmic indications.”

 

Cresset Discovery Services case studies

Cresset Discovery Services manages and delivers outsourced computational chemistry programs. We work alongside chemists to solve problems, provide fresh ideas, remove roadblocks and add direction and insight. We work on:

  • Lead generation and optimization
  • Creating, broadening or protecting IP
  • Supporting grant funding applications
  • Accelerating the commercialisation of assets.

What we actually do depends on the customer project, which is usually confidential. Our case studies give an idea of the breadth and flexibility of our work and include some anonymized examples of customer projects.

November & December 2016 newsletter

CEO end of year message

Rob Scoffin reviews 2016 which has been an exciting year of developments for Cresset.

Docking Factor-Xa ligands with Lead Finder

In this case study, two different Lead Finder docking modes (standard and extra precision) were used in docking studies on a small number of Factor-Xa (FXa) protein-ligand complexes originally used in the CSAR 2014 benchmark exercise.

Spark reagent databases

The November release of the Spark reagent databases derived from eMolecules is now available.

Elucidating binding mode and molecular interaction of new class of anti-fungal drugs

Dr Martin Slater, Director of Cresset Discovery Services, describes how modeling work was critical to predicting the binding mode of the inhibitor and important interacting amino acid residues.

Pave the way for more repurposed drugs

David Cavalla, Numedicus, argues that linking prescriptions to medical conditions would make it easier for companies to re-coup costs and open the way to market for repurposed compounds for rare diseases.

The Cresset User Group Meeting – June 29-30, 2017 – Cambridge, UK

  • June 29: Scientific program featuring invited speakers from 4 continents. Cresset in-house experts will present the latest software developments, including a showcase of our new structure-based design tool.
  • June 30: Hands-on software workshops.

Dr Scoffin, Cresset CEO, chairs and presents at International Congress of Medichem, Nanjing, China, 16-19 November 2016

Cambridge, UK – 15th November 2016 – Cresset, innovative provider of software and contract services for small molecule discovery and design, is pleased to announce that this week, Dr Robert Scoffin, CEO, will chair the ‘Sym 203: Pioneering Screening Technologies for Lead Compounds’ session at the Annual Congress of Medichem in Nanjing, China. Dr Scoffin will also present an overview of virtual screening methods for drug discovery.

The virtual screening of molecules is a commonly used technique within pharmaceutical drug discovery, and has many applications including the selection of compounds for ‘wet screening’ and the design of novel libraries of compounds.

“Cresset is a market leader in virtual screening,” says Dr Scoffin. “Blaze is an effective ligand-based virtual screening platform used by pharmaceutical companies globally. Blaze is also used by Cresset Discovery Services who carry out virtual screening in many consultancy projects. I am looking forward to sharing the various methods employed within a virtual screening cascade, including 2D methods, 3D ligand-based methods and 3D structure-based methods, and describing how each of these contributes to the overall value of the virtual screening process.”

dr-robert-scoffin
Dr Robert Scoffin