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The abstract of John’s talk is as follows:

Towards In-House Searching of Markush Structures from Patents
Well-integrated in-house ("behind the firewall") cheminformatics systems able to handle databases of individual molecules for substructure and similarity searching have been available for many years, normally in the context of Oracle RDBMS data cartridges. These systems are able to search diverse databases (including internal, bought-in, and public ones) with a single interface, and may include additional features such as physicochemical property profiling and structure-based cluster analysis. Recently some have been extended  to handle Markush representations of un-enumerated combinatorial libraries alongside discrete molecules. This paper describes ongoing work to extend them further to handle the more complex Markush structures found in patents, and discusses the issues involved in doing so, and the opportunities that may arise.

Further programme information can be found at the conference website at www.ipi-confex.com.

Product Director, Matt Wright, commented: “With its open architecture and standard SQL interface, the Torus data cartridge fulfils a need for a versatile component that can ‘chemistry-enable’ any Oracle-based application.” He added: “Our sophisticated Markush technology not only provides an effective solution for combinatorial chemistry, but also paves the way for handling structures published in chemical patents.”

In acknowledging the contributions from Digital Chemistry’s industrial collaborators, Managing Director, Julian Hayward commented: “We are especially grateful for the foresight and support of the Cheminformatics group at GlaxoSmithKline in Stevenage, not only for sponsoring the development of Torus but also for their significant input during an extensive testing phase.”

Version 1.0 of the Torus data cartridge is available now for free evaluation on Windows, Linux or Solaris platforms – an optional Windows client, Torus:View, is included, permitting searching and visualization of the results.

To view a copy of the full press release in PDF format, click here.

Digital Chemistry was chosen for its work developing innovative scientific software, the RSC’s industry specialist, Melanie Washington, said: “We are delighted to recognise the contribution made by Digital Chemistry. The chemical industry is not just about manufacturing, but also the technology and software which is vital to its success.”

About the RSC
The Royal Society of Chemistry is the UK Professional Body for chemical scientists and an international Learned Society for the chemical sciences with some 43,000 members worldwide. It is a major international publisher of chemical information, supports the teaching of chemical sciences at all levels and is a leader in bringing science to the public.

The abstract of John’s talk can be viewed below; if you are attending the meeting you can see John’s presentation at 10:15 on Monday 11th September in the Division of Chemical Information session, Challenges in Structure Searching, Room 122 of the Moscone Center.

Substructure Searching of Markush Structures and its Uses
John M. Barnard, Anthony P. F. Cook, Geoff M. Downs, Annette von Scholley-Pfab, Daniel G. Thomas, P. Matthew Wright, Jimmy Chung, Gavin Harper, and Stephen Pickett.
Direct substructure searching of Markush structure representations of large virtual combinatorial libraries offers substantial speed advantages over searching the enumerated molecules, since each individual building block needs only to be examined once. Markush substructure searching has several potential applications in the management of collections of large virtual libraries, and has been implemented in the context of an Oracle RDBMS data cartridge. The libraries can be stored as Markush structures (or as pools of precursor molecules with generic reactions) rather than as enumerated products. The presence or absence (in the product set) of substructures or complete molecules of interest can be rapidly identified, and just the relevant molecules enumerated if required. Physicochemical and ADME properties based on additive contributions from predefined sets of substructures can be rapidly calculated. Work on a recent collaborative project will also be described, in which Markush substructure search techniques are used for rapid generation of the "reduced feature graphs" (Harper et al., J. Chem. Inf. Comput. Sci., 2004, 44, 2145-2156) present in a large virtual library, and for identification of those that contain specified patterns of feature nodes, along with the corresponding individual molecules.

The new chemistry cartridge will uniquely incorporate Digital Chemistry and BCI Technology into Oracle and enable the integration of Markush Structures into Oracle based applications. Its strength lies in its ability to handle vast combinatorial libraries including the generation of Markush structures from existing compound databases.

Commenting on the potential of Torus and its many possible applications Product Director Matt Wright said "By combining the speed and sophistication of Digital Chemistry’s Markush structure handling software with the powerful and versatile environment of Oracle, Torus fulfils a long-standing industry need to store, search and analyse compound libraries, represented as Markush structures. This compact representation not only allows for efficient handling of vast compound collections but also lends itself to novel and innovative exploration of chemical space".

The Digital Chemistry website lists a number of the key features of Torus notably that it is fast and scalable, with no quantitative limits and includes search functions on substructure, exact structure, similarity and overlap of Markush libraries.
An example Markush dataset will be included with Version 1, which will support multiple standard storage formats including Molfile, SLN, cSLN, RGfile and SMILES. Structural querying is based on SMARTS with format conversion from MDL formats available.

Access will be possible using the Torus GUI or via a standard SQL interface and application development is possible in all modern programming languages.

Noting Torus’ extensibility to patent Markush, Managing Director Julian Hayward said "Torus represents the culmination of many years’ research and development effort within this crucially important but largely-unsolved area of chemical informatics. The relevance of the Markush solution as a basis for solving the chemical patent problem has not gone unnoticed and we will be making further announcements in this area in due course."

Torus will be available later this year and demonstrations can be seen at DDT 2006 in Boston in August and at the ACS Fall Meeting in San Francisco in September. If you would like more information or wish to register for email updates about Torus please contact us at info@digitalchemistry.co.uk.

Significant enhancements have been introduced to the Markush component, including the selective enumeration from a Markush structure of those specific molecules that match a specified substructure query. The handling of "reduced feature graphs" -first introduced in version 7.10- implementing ideas published by GlaxoSmithKline in 2004*  has also been improved and now allows the selective enumeration of specific molecules with a particular reduced feature graph.

The toolkit uses extremely fast Markush-processing algorithms, which offer order-of-magnitude speedups over approaches based on enumerating and separately processing each molecule in a Markush library. It also provides features for rapid calculation of physicochemical properties and topological indices and fragment-based fingerprints for the members of a library and identification of the overlap between two Markush structures.

The announcement comes just three weeks after the formation of Digital Chemistry and Managing Director Dr Julian Hayward remarked "These appointments are pivotal in enabling us to succeed in our company goals to build and expand on the scientific excellence of our wholly owned subsidiary Barnard Chemical Information (BCI)."
"Our existing customers are already aware of our outstanding consultancy services but these new appointments will enable us to build and support the world leading cheminformatics products that we are currently developing."

Digital Chemistry was incorporated on 20th September 2005 and has offices in Leeds, UK. The company's goals are to deliver sophisticated software tools and services which address the cheminformatics needs of researchers within the pharmaceutical and related industries. Initial products will be based on the well-known BCI Toolkit and will include new web services.

Managing Director, Dr Julian Hayward commented: "Digital Chemistry has been set up to focus on solving complex problems in cheminformatics and to ensure that the resulting software is delivered efficiently and effectively to our users. By joining forces with BCI from the outset, we are able to build on the excellent science already established in the BCI Toolkit while, at the same time, providing a focus for further innovation."

BCI's founder, Dr John Barnard, added: "Digital Chemistry provides an ideal vehicle with which the science and technology developed by BCI over the past 20 years can be fully exploited. I am confident that this new organisation will provide the presence to enable many more researchers to benefit from both its existing and developing technology."