December 2010 Newsletter

In this issue we have articles on Knime, the new release of MOE from CCG, plus a conference report for the recent Protein Kinases: Signalling Success 2010 meeting at Chesterford Park and an article on the patentability of DNA.

Data Pipelining with KNIME: Power to the People!

Data pipelining has been around for some time, but – judging by the starring role it has been assuming at several recent chemoinformatics & modelling meetings – it now seems to be firmly established at the forefront of many leading R&D organisations as the method of choice for disseminating predictive computational tools to scientists.

Pipelining brings applications from multiple sources into a single graphical interface, allowing chemists and biologists to regain control of property calculations, data analysis, selection of compounds for purchase, docking studies, predictive ADMET approaches….basically any task which can be performed computationally. And this seems to be going down a treat with the scientists. Mike Bodkin (Lilly) presented a talk at the Autumn UK QSAR & Chemoinformatics Group meeting at the EBI, Hinxton, where he described how widely and enthusiastically pipelining tools have been embraced at Lilly. The chemists routinely use the workflows compiled by the chemoinformatics/modelling groups, and the modellers often assume a “consultancy” role, assisting the chemists as they use the tools, and modifying the tools as needed by the chemists.


Whilst commercial pipelining options are available, such as Pipeline Pilot from Accelrys, the open-source KNIME system ( offers an excellent framework for pipelining, and many modelling software vendors now supply ready-made KNIME nodes to complement the functionality already offered through the system. KNIME comes with many nodes specific to chemical applications (eg SDF & mol2 file input & output, fingerprint creation, molecule sketcher, statistical methods) and these are complemented by the Weka nodes also distributed with KNIME which offer classification tools such as clustering & Bayesian algorithms.

Pipelining lets you pull together your chosen software tools into a user-friendly graphical tool which can be accessed by any scientist in your organisation.

For more information on pipelining with KNIME or to discuss development of tailor-made KNIME workflows contact Susan Boyd at CCS.

New MOE Release – MOE 2010.10

In the year that brought us Avatar in glorious 3D, CCG have now released their new 3D stereo version of MOE, which comes complete with its own set of 3D viewing glasses. Don’t try to watch Avatar wearing them though as it’s kind of a different system….! As well as the new mode for 3D viewing, the MOE graphics have been enhanced and accelerated throughout.

MOE 2010

The interface looks a little different too. CCG have worked closely with their clients over the last year to optimise the new interface which has been redesigned for ease-of-use.

One key new feature of the 2010 release is the kinase database browser & explorer. Over 2000 protein kinase crystal structures from the PDB have been aligned, and users can query the structure database very flexibly, based on ligand topology, receptor domain information, residues in the active site and activation state, for example.

A new NAMD interface is now in place, enabling large-scale molecular dynamics simulations to be set-up within the MOE environment.

For modellers supporting medicinal chemistry projects, the new methodology to perform rule-based medicinal chemistry transformations on structures which are docked into a receptor pocket should be of interest. Pharmacophore, synthetic tractability and physchem parametric filters can be set-up ahead of the computation to ensure that the compounds suggested are in line with expectations.

All in all the new package has been developed with the needs of MOE’s users in mind. Certainly much of the new functionality will be of interest to us at CCS.

For more information on how CCS can help your modelling efforts using the new MOE system, contact Susan Boyd at CCS.

Protein Kinase 2010: Signalling Success

Recently, the SCI-RSC hosted their 4th meeting in the protein kinase series. “Protein Kinase 2010: signalling Success” was held at Chesterford Park, near Cambridge, on 20th October 2010. The meeting was well attended by those working within the Drug Discovery and Development arena, from both industry and academia.

Despite the kinase class sometimes being associated with delivering ‘dirty drugs’, the emphasis of this meeting was to confirm kinases as clinically relevant targets following the success of kinases in the oncology market, (e.g. Tarceva from Roche), and also to demonstrate the potential for kinase inhibitors in other therapeutic indications in the future.

The day-long meeting consisted of a series of talks given by industry representatives, covering detailed approaches to inhibition of CDK, Aurora-A, ChK, IKK2 and MAPKAPK-5 kinases for a variety of therapeutic indications, including rheumatoid arthritis and COPD.

The morning and afternoon sessions were both opened with a plenary lecture; the first of which was given by Gerhard Muller of Proteros. Gerhard’s talk concentrated on fragment-based approaches and optimisation of post-Lipinski’s parameters. He illustrated the alternative drug design approach to that of traditional Medicinal Chemistry, drawing attention to concentrating on the ‘deep back pocket’ first, in order to improve selectivity.

In summary, the advances in the understanding of how protein kinases work are leading to improved drug design. From listening to all of the talks, it is evident that protein kinase inhibitors remain a very active area, potentially delivering many new drugs against a range of indications over the next decade.

To discuss medicinal aspects of kinase inhibition, or for more general information on medicinal or CMC chemistry please contact Andrea Walmsley at CCS.

Gene Patents a thing of the past?

A recent article in Chemical and Engineering News 1 highlights the recent total about face on the patentability of unmodified genomic DNA. This announcement will add to the growing debate about the merits of patenting anything connected with living organisms and who should be able to own Intellectual Property rights in such circumstances.

The ruling by the U.S. Justice Department reverses decades of government policy, declaring that “products of nature” which it considers genes to be, cannot be protected by patents. This landmark lawsuit challenged patents by Myriad Genetics and the University of Utah Research Foundation on the genes BRCA1 and BRCA2, which are involved in increased susceptibility to breast or ovarian cancer. This high level ruling ends a lengthy process involving U.S District Courts 3 and goes against the previous US Patent Office policy, and that adopted by the US Nation Institute for Health and other government agencies which have applied for patents protecting the intellectual property relating to similar kinds of inventions.

While modified or recombinant DNA will still be patentable, the policy change will have a significant effect on both biotechnology companies and Universities. Clearly for academic institutes it has the potential to signal the end of promising lines of research because protection of Intellectual property is essential for research projects to progress from the University Laboratory to fully developed medicinal products backed by well funded Pharmaceutical companies.

This ruling in the United States could well lead to other governments and Patent Offices around the world to re-examine the patentability of genes, DNA and other biotechnology products. However in Europe the battle has lasted for a number of years and University of Utah patents on BRCA1 revoked in 2004 by the European patent Office were re-instated in 2008 2.

This is a controversial area since biotechnology companies charge for diagnostic tests relating to BRCA1 genes amongst others and if the technology were no longer patentable the cost could well reduce, as it does when generic competition enters the prescription medications market.

If you need advice about protecting a discovery or invention, or just want to explore what the options are then please contact Neil Walden at CCS.

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