1/18 GLIDA: GPCR-ligand database for chemical genomic drug discovery Reporter: Yu Lun Kuo Date: November 28, 2006 Yasushi Okuno*, Jiyoon Yang, Kei Taneishi, Hiroaki Yabuuchi and Gozoh Tsujimoto Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto , Japan Nucleic Acids Research, 2006, Vol. 34, Database issue

2/18 Outline Introduction Data Contents GPCR & Ligand Search –Similarity Search Web Site Interface & Application Conclusion & Future work

3/18 Introduction (1/2) G-Protein Coupled Receptors (GPCRs) –One of the most important families of drug target in pharmaceutical GPCR-LIgand DAtabase (GLIDA) –Novel public GPCR-related chemical genomic database –Primarily focused on the correlation of information between GPCRs and their ligands

4/18 Introduction (2/2) GLIDA –Includes structure similarity search functions –Provide correlation maps linking the search homologous GPCRs with their ligands –Contains biological information on GPCRs and chemical information on ligand compounds –Easily retrieve information from either biological or chemical starting points

5/18 Data Contents GLIDA contains three types of primary data –Biological information on GPCRs –Chemical information on their ligands –Information on binding of specific GPCR-ligand pairs

6/18 GPCR Search The general information of GPCR contains –Gene names –Family names –Protein sequences –Links to other biological databases GPCRDB, Uniprot, IUPHAR, Entrez Gene and KEGG

7/18 Ligand Search The general information contains –Names –Molecular structures –CAS registry numbers (CASRN) –Formulas –Molecular weights –MOLfiles –Links to the other chemical database KEGG, PubChem and ChEBI

8/18 Binding of GPCR-ligand pairs The correlation information relation GPCR to particular ligands –Stored in a relational database GLIDA allows users to retrieve GPCR- ligand binding information dynamically and continuously

9/18 Similarity Search GLIDA has a structure similarity search function on its result pages –Alignment scores of protein sequences generated by the BLAST –Top 25 most similar GPCRs are retrieved and listed with their similarity scores on an analytical report page

10/18 GLIDA Web Site u.ac.jp/services/glida/ u.ac.jp/services/glida/

11/18 GPCR Search by Phylogenetic tree GLIDA ID of the ligand CAS registry number

12/18 GPCR Search by Keyword Click to view its result page

13/18 Ligand Search Classification Tree Information of the Ligand Information of the GPCRs of the ligand

14/18 Ligand Search by Keyword Name GLIDA ID CAS Registry No. Synonym

15/18 Similarity Search Function The 25 GPCRs which are most similar to the selected GPCR GPCR-Ligand correlation map

16/18 GPCR as Drug Target ClassificationTargetConditionDrug name/Company name selling price / $ (hundred million) Dopamine Serotonin antagonist GPCR 精神患者 Zyprexa (Ely Lilly)17 Histamine antagonist GPCRAllergyAllega (Aventis)13 Adrenaline blocker GPCR 高血壓 (Glaxo Smith Kline)9 Serotonin agonist GPCR 頭痛 Imitrex (Pfizer)6 Histamine antagonist GPCRAllergyZyrtec (Novartis)5.5 Angiotensin blocker GPCR 高血壓 Lotensin (Pfizer)5.4

17/18 Future work GLIDA will be updates continuously GLIDA will be combined with a system for predicting novel ligands of orphan GPCRs Plan to carry out XML publication of GLIDA

18/18 Unique Characteristics of Website GPCRDB

19/18 Thanks for your attention

20/18 NAR Web Site l34/suppl_1/index.dtl#EDITORIALhttp://nar.oxfordjournals.org/content/vo l34/suppl_1/index.dtl#EDITORIAL