CNA (UK) 40th Anniversary

Next year sees the 40th anniversary of the foundation of the Chemical Notation Association (UK). The CNA was founded in 1965 in the US and the inaugural meeting of the UK chapter was on Tuesday 11 November 1969 at Fisons Pharmaceuticals in Loughborough. Ernie Hyde was the Acting Chairman and Graham Palmer the Acting Secretary. A few people present, including Wendy Warr, were already members or associate members of the parent CNA.

The CNA (UK) was renamed as the Chemical Structure Association (CSA) in 1982. The CSA Trust was founded as a separate organisation in 1988, and the Trust took over all the responsibilities of the CSA in December 2002, when the CSA was formally disbanded.

Trustees Wendy Warr, René Deplanque and Johnny Gasteiger enjoying the ACS Spring meeting in New Orleans

Sandy Lawson gets Mike Lynch Award

Professor Dr Alexander (Sandy) Lawson graduated from St Andrews University, Scotland, in 1966 with a first class honours degree in Chemistry. He went on to study at Imperial College, London, where he was awarded a PhD and DIC in 1970. He held a number of positions including research fellowships at the Universities of Kent and Mainz, directorships at the Beilstein Institute from 1982 to 1994, and subsequently directorships at MDL. He is currently Director of Research and Development at Elsevier Information Systems GmbH. Sandy has made major contributions to the fields of chemical information handling and chemical structure representation, in particular in the development of the Beilstein database and software (including the famous Lawson Number for indexing chemical structures).

The CSA Trust Mike Lynch Award is given on a triennial basis, consisting of $5,000 and an appropriate memento. The purpose of the Award is to recognise and encourage outstanding accomplishments in education, research and development activities that are related to the systems and methods used to store, process and retrieve information about chemical structures, reactions and properties.

Thomas Christopher Wrigley MRSC 1935¬¬–2007

Chris Wrigley passed away in November 2007, aged 72. He was a founder member of the Chemical Notation Association (UK) in 1969, when he worked for Wellcome Research Laboratories. He was appointed to the Wiswesser Rules Subcommittee the same year. In the early 1970s, he joined Derwent Publications (now Thomson Reuters).

Chris graduated from Cambridge University. He lived in Westerham with his wife, Fenella, and a daughter and a son, both of whom followed in their father’s footsteps by going up to Cambridge. Chris loved gardening, and grew most of his own vegetables, flowers, cacti and fruit the organic way. He was a plant collector and a great advocate for saving the environment and its resources. His cacti, peppers and tomatoes often graced Derwent office window ledges.

Freda Simoes of Thomson Reuters remembers that he was a fount of knowledge: his clear, distinct voice carried in her small, quiet office when quite often he debated technical ideas with Gez Cross, Tony Ferns or John Coleman. He did like Derwent abstracts to be correct. Sadly, he had to take early retirement, about 25 years ago, after a stroke.

People and Places

Congratulations to Barrie Walker, whose elder daughter Rosalind gave birth to a baby girl (Sophie Ann) on 21 December 2007. Barrie now has two grandchildren (see People and Places, Issue 16).

Bill Town has now three grandchildren. The latest is Emilia Mackman, born 3 January 2008, to Bill’s elder daughter Helen, and her husband Chris Mackman. Bill’s other two grandchildren are Matt’s son Joseph (born 16 June 2006) and Amy’s daughter Ella (born 21 August 2007).

Congratulations also to Clive and Lisa Dickens who got married on Saturday 10 May. Clive currently works for Accelrys UK at the Cambridge Science Park.

Congratulations to Valentina Eigner-Pitto of InfoChem and her husband Markus on the birth of Christian Michael Eigner, on 7 December 2007.

Phil McHale has taken a full-time account management position within CambridgeSoft. Still based in California, he is responsible for the west side of the USA (northern California, Oregon and Washington) and Canada (western provinces).

In moves signalling Chem-Axon’s increased focus on business development and market position, Alex Drijver has been appointed CEO, while Ferenc Csizmadia, founder and former CEO, becomes Chairman and Head of Research and Development. Alex was formerly CEO and CFO of ThalesNano, and CFO of ComGenex.

Symyx Technologies has promoted Trevor Heritage to President of Symyx Software. Trevor succeeds Timothy Campbell, who will be leaving the company to become CEO of a privately-held supply chain solutions software company.

Krisztina Boda has been a senior scientific developer with OpenEye Scientific Software since the autumn of 2007.

Chemical Structure Databases: at the Crossroads of Description and Design

‘Scientific Method’ is an essential tool for progress in science, in particular in experimental disciplines such as biology and chemistry. The iterative process of observation, hypothesis¬-building/modification and experimental testing aims to yield coherent models that are acceptable until such time as a reproducible experimental contradiction is encountered. At this point the model in question must be modified or abandoned. Thus the search for such contradictions has a high priority in scientific research, particularly in areas seeking to expand and use knowledge.

The incidence of contradictions in an area of study is a measure of the maturity of the current models, and can herald a transition from ‘description-oriented’ (fundamental) approaches to more ‘design-oriented’ (technological, predictive) approaches. The positions of ‘science’ and ‘technology’ tend to blur in the course of time, and this is particularly noticeable in societies with traditional attitudes to academic and industrial research. In my view, this transition (in the direction of design) is well advanced in the core disciplines of organic and especially medicinal chemistry, and is at the heart of the title used here.

The collected archive of all published work (the primary literature) makes no such distinction: it is the single arbiter for both descriptive models and design methods. However, researchers cannot keep a fully current awareness of all published work without using secondary indexing databases. When such databases become the main route to searching the literature, they must mirror the essence of the underlying published work, whether hypothetical models or design methodology. A number of questions can then become critical for such secondary databases. In particular, should they:

• specialise either in description-oriented or design-oriented aspects (record the models as proposed, the observed experimental results, or both)?
• attempt to bring their entire corpus into scientific self-consistency on an ongoing basis, as practised in the entire history of the Beilstein Handbook?

These questions reflect the ongoing dichotomy with respect to ‘bibliographic’ and ‘factual’ databases, and their inherent tendency to aspire to cover both areas. Irrespective of the validity of such boundaries, the dilemmas and challenges are real. Only time will give answers to these questions. However, a focus on organic chemical structures invites comment here.

Chemical structure and its diagrammatic representation have been core objects in chemistry for at least 150 years. It is probably fair to state that the nature of organic chemical structures per se is no longer a hot subject for the application of the Scientific Method. Atomic models and properties are adequately understood; definitions of valence models are no real mystery (at least for the non-metallic elements); functional groups and scaffolds usually behave in a predictable manner that allows for the wide application of generalisations suitable for education and communication. Chemistry is richly sown with such generalisations about structural features, and a plot of discovery against time would probably be relatively heavily weighted towards reports over 50 years old. Chemistry is indeed a very mature science/technology, at least with respect to small molecule chemical structures.

So, for the aspect of description of structures, is it fair to conclude that the task for databases has reduced to a relatively straightforward listing (i.e., documentation) of the structures that have actually been studied? In the context of this article the answer is surely ‘yes’, and these are increasingly publicly available, as shown by the current listing of over 18 million compounds in PubChem as one example.

Despite relegation from the cutting edge of science, interest in structural form is increasing alongside the increasing size and complexity of the structures . One factor is the relationship between form and function. In 1896, Louis Sullivan (architect) said:

‘It is the pervading law of all things organic and inorganic ... that form ever follows function. This is the law.’

Applied to chemistry, Sullivan’s dictum would turn our traditional learning process completely on its head. We learned:

‘If it has the form of a ketone, it will then function like a ketone (e.g., will undergo all the usual reactions of ketones, including the McMurry reaction).’

If he had been a chemist, Sullivan could have said:

‘I need steric constraint in a particular double bond to achieve the specific function needed in my molecular design (e.g., selectivity in a particular interaction at a cell membrane) and I can get that from the McMurry reaction of hindered ketones.’

The difference between these two approaches is the difference between description and design, essentially between documentation and innovation.

Here we have the rub for the traditional structure databases: mere documentation is no longer enough; innovation and design must be fostered. Research is ultimately concerned with new findings, with novel functionality. Such functionality is then logically expressed in a form (i.e., a structure) that is itself novel and waiting to be made, probably by analogy to existing knowledge. The systematic power of parallel syntheses helps, but the underlying elements of synthetic design and molecular design are still the domain of the scientist and the ultimate drivers of value. Therefore the scientist’s reasoning is almost certainly guided by the Sullivan type of approach, assisted by the power of analogy. Like the man said: it’s the law.

So for the design of structures, the challenge for structure databases lies in helping (via analogy) the creation of novel functionality. The novel structural form will then follow. Design is the key to solutions to problems in practice, and structure databases should enable solutions. To do this effectively, they will need much tighter interoperability with the original literature, perhaps even to the extent (to paraphrase McLuhan) that ‘the Document IS the Database’. All in all, it will be very interesting to observe the reactions of the major structural databases in this respect in 2008 and beyond.

The author would like to express his gratitude to Dr Torsten Hoffmann (Hoffmann-La Roche) and Dr Graeme Robertson (Siena Biotech) for their friendly support and helpful discussion.

Sandy Lawson Elsevier Information Systems GmbH, Frankfurt

Cheminformatics Implications of Collaborations between Academia and Industry

The CINF/CSAT joint symposium at the ACS Spring meeting in New Orleans was organised by Wendy Warr, and took a broad approach covering IT, legal, business and cultural aspects of collaboration, where relevant to cheminformatics. The symposium fitted in nicely with another CINF symposium entitled ‘Cheminformatics: from Teaching to Research’ that was organised by Alex Tropsha and Alexandre Varnek.

Can innovation from industry find broader application?

Fangqiang Zhu and Dimitris K. Agrafiotis, Johnson & Johnson Pharmaceutical Research & Development, Exton, PA,USA

The interplay between academia and industry typically involves creative scientific ideas from the academic side and practical applications from the industrial side. However, innovative ideas also originate from industrial settings occasionally. The problem then arises how such innovation can benefit the broader scientific community. In this talk, one such example was presented, where the pursuit of certain applications of a novel computational method generated in a commercial company may lie beyond its direct commercial interests.

Rewards and challenges of academic–industrial collaborations in the area of computational drug discovery

Alexander Tropsha, Laboratory for Molecular Modeling, School of Pharmacy, University of North Carolina, NC, USA

Alexander Tropsha has over 15 years experience of collaborations with various pharmaceutical companies in the areas of computational drug discovery research and graduate education. The rewarding aspects of collaborations included access to real data and projects (certainly under strict confidentiality agreements), intellectually stimulating discussions with industrial colleagues, opportunities to test academic software in industrial settings, and networking that helped in a number of cases with the job placing of graduate students and post-doctoral students. In the area of graduate education, students benefited in many cases from industrial internships, lectures by industrial colleagues, and their services on students’ advisory committees. Challenges included difficulties with data exchange, restrictions on publications, and instability of projects.

Academic–industrial collaboration in chemoinformatics: experiences from the UK

Valerie J. Gillet and Peter Willett, Department of Information Studies, University of Sheffield, Sheffield , UK

The Chemoinformatics Research Group at the University of Sheffield has extensive experience of collaboration with industry over many years. Collaborations have varied from the provision of software and databases via collaborative MSc and PhD projects through to fully funded post-doctoral positions within the research group. The different mechanisms through which collaboration has been achieved, some success stories and the ingredients for success were discussed.

University–industry collaborations: the good, the bad, and the ugly

G.M. Maggiora, Pharmacology & Toxicology, College of Pharmacy & BIO5 Institute, Tucson, AZ, USA

Having spent time in both universities and the pharmaceutical industry, Gerry Maggiora has seen a number of issues regarding collaborative research from both points of view. Over the past 20 years, industrial and university research has changed significantly. This is not only due to revolutionary changes in basic science and technology, but also to changes in the roles that research is playing in both of these regimes and in the way that research is funded there. This raises a number of questions. Is there any value in industry–university collaborations? If so, is this value currently being realised? If not, why not? What role(s) are evolving industry and university research practices playing in current industry–university relationships? What can be done to strengthen industry–university collaborations?

Both sides now: an intimate perspective on collaborations

Robert D. Clark, Informatics Research Center, Tripos International, St. Louis, MO, USA

Tripos has engaged in several major collaborations over the past decade. In some of these, Tripos played the role of industry supporter and in others it was essentially the academic partner. Sometimes these collaborations have led to the development of commercial software products; sometimes they have advanced science in fairly basic ways; sometimes they have done both, directly or indirectly. Experience garnered along the way is worth sharing inasmuch as it may shed light on what makes such collaborations succeed and what can make them fail.

Gunter Grethe and René Deplanque know what helps a successful exchange of ideas along

Networking universities of applied science with small and medium-size enterprises: new applications of semantic systems

René Deplanque, Professor, Director, FIZ-CHEMIE Berlin, Berlin, Germany

One of the main problems in the area of technology transfer is the different approach which universities take compared to that chosen by small and medium-size companies. For example, when evaluating of the usefulness of a newly found substance, universities are mainly interested in the physical and chemical properties of the compound, whereas small and medium-size companies are far more interested in the usage and the market potential. Because of these different approaches, it is very difficult to breach the gap in understanding of the priorities between those two groups.

Knowing the difference in priorities, a ranking can be defined, which takes into consideration how a problem is approached and how results can be presented to be useful to both sides. Combining semantic, graphical, full text and qualified list searches, it is possible to serve both approaches, without asking the user to learn complex databank languages. This should increase the chance of new and successful projects in which the different points of view are used to strengthen the project approach.

Community-based collaborative drug discovery for neglected infectious diseases

Barry A. Bunin and Sylvia Ernst, Collaborative Drug Discovery, Inc., Burlingame, CA , USA

Scientists are successfully working in secure collaborative groups to rapidly develop drug candidates for commercial and humanitarian markets. A case study involves overcoming drug resistance, which is the major problem for malaria. New approaches that allow scientists working together to develop new drugs faster are desperately needed. The discovery of alternatives to Verapamil, a known chemosensitiser for overcoming both tumour and malaria resistance, was presented using novel collaborative drug discovery technologies to help specialists work together in a global network. A example showing how chemosensitisers addressing chloroquine resistance can be identified combines results from the University of Cape Town (South Africa) with structurally related compounds from the University of California at San Francisco (USA) and similar FDA/Orphan (courtesy Dr Lipinski) approved drug compounds. This new collaborative technology allows researchers to build up networks of technical experts around therapeutic or target areas, thus facilitating discovery of new drug candidates. It allows scientists to speed up the research by simultaneously sharing unpublished data in the race to overcome drug resistance. The community-based platform is currently being used openly to help develop new treatments for neglected infectious diseases such as malaria, Chagas Disease, and African Sleeping Sickness, and securely against commercial cancer targets.

Experiences with knowledge and data sharing at Lhasa Ltd

Philip N. Judson, LHASA Ltd, Department of Chemistry, University of Leeds, Leeds, UK

Lhasa Ltd was originally set up by organisations wanting to share knowledge about chemical synthesis. Over the years, the sharing has broadened to cover toxicology, mammalian metabolism and environmental biodegradation, and to include data as well as knowledge. Chemical and biological information are closely associated in these fields, and chemoinformatics cannot be confined to the realm of chemistry. Problems arise over standardisation of terms, methods of assessment and interpretation of data. Issues over confidentiality and security have to be addressed, and there are tensions between the needs of academic groups to publish and those of industrial groups to protect intellectual property rights.

Safe exchange of chemical information: not ‘safe’ enough?

Tudor I. Oprea, Division of Biocomputing, Department of Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, NM, USA

An ACS symposium dedicated to the safe exchange of chemical information (SECI) was held in San Diego in Spring 2005; of the 16 speakers, 11 contributed papers to a special issue of J. Comput.-Aided Molecular Design (JCAMD; Nov 2005). Despite the scientific enthusiasm, as well the potential solutions proposed, the SECI initiative was not well received in industrial circles. Indeed, there has been no follow-up from a business or scientific perspective. A number of the JCAMD papers offered solutions (and examples) and illustrated how SECI is possible. However, it was perception, not fact, that has resulted in a general lack of interest from potential industrial partners. This presentation looked at some of the potential solutions, and off-the-record responses from potential industrial partners, with respect to the safe exchange of chemical information.

Using SemanticEye and FOAF to add value to the scientific collaboration process

Henry S. Rzepa, Department of Chemistry, Imperial College London, UK, and Omer Casher, GlaxoSmithKline, Harlow, UK

Metadata embedded within electronic publishing resources can be combined with user profiles in Web 2.0 resources (blogs, wikis and social networking sites), to create a single entry point for enhancing scientific collaboration. Enabling such activities is one of the goals of Web 3.0, which represents the next evolutionary step in the web cycle. It is predicated on the adoption of a semantic web approach to content management. This presentation offered a proof of concept featuring two tools:

• SemanticEye, a lightweight ontology of chemical electronic publishing metadata which enables the location of articles by the same author or containing the same molecule (as determined using InChi identifiers)

• FOAF, the ‘friend-of-a-friend’ RDF vocabulary which we propose be used for the social networking aspects.

FOAF allows semantic expression of an individual’s publications, public collaborations and activities. FOAF aggregators are software agents which are used to build up a network of ‘friends’ akin to the goals of social networks such as open-Notebook Science and LinkedIn, but in an automated fashion. Rather than rely on an individual creating and maintaining their own static FOAF, we propose a more dynamic approach to the FOAF metaphor, in which SemanticEye is used to output a FOAF serialisation of its ontology by querying it with SPARQL, the RDF query language, and FOAF information from other sources, such as our Scientific seminar RDF/RSS database. Institutional or departmental digital repositories can similarly be queried and then aggregated with the SemanticEye FOAF. This FOAF aggregation could feed into any social network which is RDF/FOAF compliant, and then subjected to further SPARQL queries to create a semantic fusion between molecules, publications and scientific collaborations.

IUPAC Computer Readable Chemical Reaction Database Standards

A project to develop a standard representation for chemical reactions was launched recently at a meeting in Berlin, Germany, hosted by René Deplanque of FIZ Chemie. The project is being led by Guenter Grethe.

The goal of this meeting was to develop the requirements for a proposal to be submitted to IUPAC to fund an Open Source, public domain ReactionML (IUPAC RML) standard to complement the IUPAC InChI chemical structure representation. The requirements would include what the community needs, technical and organisational issues and financial aspects.

The meeting was quite successful and an initial first stage of the project was agreed to and will include:

• Reactants
• Products
• Reagents
• Catalysts
• Solvents

All the chemical structure representation will be based on and build upon the IUPAC InChI/InChIKey standards, which, since its introduction in August 2006, has become the international chemical structure representation standard for all large databases of chemical data. Some of these databases containing InChIs are in excess of 36 million unique structures.

It is expected a beta test release version of this new IUPAC standard will be available for public testing by the end of 2008.

Steve Heller

New Secretary & Committee Chairs

At the 2007 Annual General Meeting in December, David Walsh retired as a Trustee of the CSA Trust. We welcome Trustee Bonnie Lawlor (pictured) as our new Secretary.

Christoph Steinbeck is the new Chair of Meetings and Training, and Guido Hermann becomes Chair of Fund Raising.

Travel Grants awarded

Maciej Haranczyk is to receive the 2008 CSA Trust grant to travel to Sheffield University, Sheffield, UK, for a 6-week visit. Maciej is a Master of Science in Physical Chemistry, University of Gdansk, Poland, and is currently undertaking Doctoral studies on the field of computational chemistry, also at the University of Gdansk.

He will to travel to Sheffield in order to learn the techniques required for processing large databases so that he can scale-up his hybrid combinatorial chemistry/quantum mechanical chemistry/chemoinformatics approach to molecular design. While at Sheffield, he will also carry out a small-scale project that will demonstrate the practical implementation of the techniques developed to date.

A further £1000 bursary has been awarded to Sheffield University students to assist with travel for 13 research students to attend the 8th International Conference on Chemical Structures in Noordwijkerhout conference this June.