1. The Grid in a Combinatorial Laboratory Jeremy Frey Department of Chemistry University of Southampton

2. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Bristol Chemistry ECS Stats Chemistry Combi Centre Southampton IUPAC RSC IBM CCDCCCDC PfizerPfizer IT Innovation CombeChemCombeChem GSKGSK AZAZ NCS

3. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Design Automation Analysis Structures Models Properties Experiment

4. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Comb-e-Chem Vision A Pervasive Grid-Based e-Science Environment Structures DB Properties DB Simulation and calculation Structure + PropertiesKnowledge + Prediction

5. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Pharmaceutical Salts S.C. Ward Salts allow the properties of the solid forms to be modified without altering the biochemical properties of a drug. Selecting the best salt form for an ionisable drug is now of paramount importance in the pharmaceutical development of new chemical entities. No accepted procedure for selecting such a form during the drug development process.

6. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton One such parent acid is succinic acid, it is a pharmaceutically acceptable acid and can exist in two polymorphic forms. In each case the succinic acid molecules are linked into zigzag chains by strong O-H….O hydrogen bonds.

7. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Salt Screen More often than not, salts selected on a practical basis, such as previous experience with the salt type, ease of synthesis, percentage yield, etc. A detailed systematic study of organic salt formation is required to enhance our understanding of all the factors that affect salt formation. The process of identifying chemical space begins with the choice of descriptors.

8. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Salt Formation Space S.C. Ward, D. Woods, S.M. Lewis, M.B. Hursthouse A variety of traditional descriptors have been investigated along with BCUT descriptors. Use Design of Experiments (DoE) statistical techniques to ensure coverage of the space with a reasonable size sample. Still lots of experiments Need high throughput automated crystalography

9. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton National Crystallography Service: NCS SYNTHON Project Voronoi Project Single Crystal Structure Determination Powder Diffraction Single Molecule Shape Determination Property Prediction Services Structure Determination Services

10. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton user NCS technician Audio VNC monitor control VNC ideal for connecting existing programs technician LAB Office VNC Control Audio

11. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton VNC Web Service VNC Client PC Equipment PC VNC Server Firewalls Web Service Proxy Tunnel End point SOAP RFB Tunnel RFB over SOAP Equipment PC VNC Server

12. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton

13. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton NCS Lab Service

14. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton NCS Scenario (1)

15. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Sample Processing (X-ray Experiment (1))

16. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton User Authorisation (X-ray Experiment)

17. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Portal Access

18. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Public / Private Key Encryption A subscriber generates a key pair comprising a complimentary private and public key The private key is kept strictly private The public key is distributed to anyone its owner wishes to communicate with When the public key is used to encrypt data, only the private key may decrypt this data

19. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Certificates A certificate comprises: a public key an identity assertion for Combechem, this is in the form of an X.500 Distinguished Name (DN) a signature of a trusted authority asserting: the validity of the public key the validity of the identity assertion that the public key is the one generated by the person represented in the identity assertion for Combechem, this trusted authority is the Combechem Certificate Authority (CA)

20. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Use of Certificates The Certificate performs two main functions: secure communication through encryption using its public key positive identification of the Subscriber through the identity assertion the DN in the certificate is used as an identifier for the Subscriber in the sample tracking database The Certificate’s integrity is vouched for through the the CA’s signature The Certificate is distributed to all parties with whom its owner wishes to communicate

21. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Remote interaction Remote control of equipment Interaction with people & equipment Security Issues Authentication and Authorisation within and across organisations Safety Critical Systems External & Internal control of systems can lead to safety conflicts Mission critical software (avoid at this stage)

22. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Laser x-ray single molecule scattering High Power LaserX-Ray Target Interlock Systems Safety

23. Analysis Structural Similarity & Difference Graham Tizard & Thomas Gelbrich

24. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Develop process on few Apply to the whole library Synthesis, analysis, measurements Design of experiments

25. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Full combinatorial space polymorphs Salts

26. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Influence of electrostatic potentials on the formation of a non- centro-symmetric member of a set of polymorphic crystal structures Polymorphic FamiliesG. Tizard

27. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Unit cell parameters and isostructurality

28. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton

29. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Unit cell parameters and isostructurality Check the atomic coordinates!

30. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Synthon C omparison Molecules Crystal Structures A A Space group Unit cell Atom lis B B Space group Unit cell Atom list Conventional crystal structure parameters do not support the analysis of packing similarities!

31. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton C omparison Molecules Crystal Structures A A Space group Unit cell Atom list Alternative parameters B B Space group Unit cell Atom list Alternative parameters Analysis Synthon

32. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Sulfathiazole T. Gelbrich: The SYNTHON Project 1/3

33. Prototype

36. 0D: Dimers I = (pseudo*)- inversion R = (pseudo*)- rotation III I I I*II I I*II I I*II I I I R* I I II R*,R* II R* II I I I II II / / R* II II / I II / II / I / R* I /D / I R* / II I I I

37. Type A Type B A A AA A A A A A AB A A A 1D: Chains AB A A A

38. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton The Synthons of Sulfathiazole III, IV, V I A single sheet 2D II AB double sheet 2DIII AA double sheet 2D Sulfathiazole V III IV Polymorphs ABABABABABABABABAABBAABBAAAAAAA

39. Back to the Laboratory If information is destined for the Grid then this should be implicit from the beginning.

40. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Pervasive Computing and the Laboratory Grid Automatic capture of metadata Sample tracking Conditions monitored Data recorded Relational Databases common in industrial research not so in university Room/People/Experiment Types of information

41. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Databases Database will become the key method of handling all data Metadata must be generated at inception and added as data traverses the workflow Version control, audit and backup handled at the database level. Change in the outlook of most bench chemists

42. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Metadata material Batch no. Identifier Supplier db process measure Lab databaseSafety db In the Grid world the databases are distributed not local copies Need a language to convey all details in a standard manner XML cf CatML description of catalysts - IUPAC role

43. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Second Harmonic Generation Used to study liquid surfaces and liquid- liquid interfaces Model membranes for industrial and biochemical processes. Used to develop the tight coupling of design – experiment – analysis. Results of one experiment modify the procedure used in the next.

44. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Second Harmonic Generation a liquid liquid interfaces under electrochemical control

45. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Polarisation dependence of SHG signal 0 20 40 60 80 100 120 140 160 180

46. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Raw laser signal

47. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton High throughput – close coupling DesignAnalysis Experiments Statistics using R Open Source Works with XML Databases

48. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton Journals: Publication @ source Journal MaterialsDatabaseMultimediaLaboratory DataPaper “Full” record

49. Reality Grid Workshop 18 June 2003 Jeremy Frey, Department of Chemistry University of Southampton People Mike Hursthouse, Thomas Gelbrich, Graham Tizard, Susana Ward, Mike Surridge, Sue Lewis, Dave Woods, Simon Coles, Mark Light, Lefteris Danos, Steve Taylor, Ken Meacham, Ann Bingham, Dave de Roure, Graham Smith, Hugo Mills, Alan Welsh