Est. 1993, ~4,000 users/month1 The G protein-coupled ... · Est. 1993, ~4,000 users/month1 The G...
1
GPCRdb.org Est. 1993, ~4,000 users/month 1 The G protein-coupled receptor database GPCRdb 1,2 Christian Munk *, Albert J. Kooistra, Gáspár Pándy-Szekeres, Stefan Mordalski, Tsonko M. Tsonkov, Kasper Harpsøe, Alexander S. Hauser, David E. Gloriam Department of Drug Design and Pharmacology, University of Copenhagen, Denmark *[email protected] 1) Munk, C. et al. British Journal of Pharmacology, 2016, 173(14), 2195-207 2) Pandy-Szekeres, G. et al. Nucleic Acids Res, 2018, 46 (D1), D440-D446. 3) Isberg, V. et al. Trends Pharmacol Sci, 2015 36(1), 22–31 4) Munk, C. et al. Current Opinion in Pharmacology, 2016, 30, 51-58. Genetic variation 6 Drugs 7 • Genetic variation in 60K humans • Genetic variation statistics • Receptor variant browser • Estimated economic burden • Post-translational modifications • Commercial availability • GPCR ligand browser 1 • GPCR ligand statistics • >140K ligands from ChEMBL • >280K experimental data points • Ligand bioactivity profiles OH O N H HN OH O P O P U L A R Structure-based alignments 3 • Helix bulges/constriction gaps • Residue conservation statistics • Generic residue numbers 3 • Custom colouring • Download for publication Residue diagrams Structures • Structure browser • Structure statistics R E C E N T L Y P U B L I S H E D Binding site mutations 4 Ligand database 2 Homology models 2 Structure determination resource 5 Signalling protein resource • Complex structures analysing tool • Align multiple interfaces to whole GPCR class • Models for whole GPCRome • Position-specific rotamer libraries • Multiple X-ray templates • Diff. conformational states • GPCR drugs browser • GPCR drugs statistics • Primary/secondary targets • Disease indications • Clinical progression • NHS prescription data 3 Established targets Targets in trials I N D E V E L O P M E N T Structure comparison resource 8 • Intra-GPCR residue-residue interactions • Residue angles and properties • Compare interactions within or between sets of GPCR structures • Identify unique and conserved interaction patterns • Interactive visualization tools linked with a 3D protein viewer • >30.000 mutagenesis data points • Mutant design tool • Coupling data from Inoue et al., 2019, and Guide to Pharmacology • Browse experimental data and constructs • Construct design tool • Thermostabilising mutation suggestions Experiment Browser Funding N E W O N L I N E • GPCR–G protein models • Based on newest structures Web: www.GPCRdb.org Email: [email protected] @gpcrdb Contact Find these resources under the Signal Proteins menu option on gpcrdb.org Arrestin and G protein pages Complex homology models Coupling data Interaction matrix • Find publication ready diagrams • Overlay with other data sources (PTM, Variants etc) References 5) Munk, C. et al. Nat Methods, 2019, 16, 151–162. 6) Hauser, A. S. et al. Cell, 2018, 172 (1-2), 41-54 e19. 7) Hauser, A. S. et al. Nat Rev Drug Discov, 2017, 16 (12), 829-842. 8) Access given upon request
Transcript of Est. 1993, ~4,000 users/month1 The G protein-coupled ... · Est. 1993, ~4,000 users/month1 The G...
GPCRdb.org
Est. 1993, ~4,000 users/month1
The G protein-coupled receptor databaseGPCRdb1,2
Christian Munk*, Albert J. Kooistra, Gáspár Pándy-Szekeres, Stefan Mordalski, Tsonko M. Tsonkov, Kasper Harpsøe, Alexander S. Hauser, David E. Gloriam
Department of Drug Design and Pharmacology, University of Copenhagen, Denmark*[email protected]
1) Munk, C. et al. British Journal of Pharmacology, 2016, 173(14), 2195-207
2) Pandy-Szekeres, G. et al. Nucleic Acids Res, 2018, 46 (D1), D440-D446.
3) Isberg, V. et al. Trends Pharmacol Sci, 2015 36(1), 22–31
4) Munk, C. et al. Current Opinion in Pharmacology, 2016, 30, 51-58.
Genetic variation6 Drugs7
• Genetic variation in 60K humans• Genetic variation statistics• Receptor variant browser• Estimated economic burden• Post-translational modifications
• Commercial availability• GPCR ligand browser1
• GPCR ligand statistics• >140K ligands from ChEMBL• >280K experimental data points• Ligand bioactivity profiles
OH
O
NH
HNOH
O
POPULAR
Structure-based alignments3
• Helix bulges/constriction gaps• Residue conservation statistics• Generic residue numbers3
• Custom colouring• Download for publication
Residue diagrams Structures
• Structure browser• Structure statistics
RECENTLY
PUBLISHED
Binding site mutations4
Ligand database2
Homology models2
Structure determination resource5
Signalling protein resource
• Complex structures analysing tool• Align multiple interfaces to whole GPCR class
• Models for whole GPCRome• Position-specific rotamer libraries• Multiple X-ray templates• Diff. conformational states • GPCR drugs browser
• GPCR drugs statistics• Primary/secondary targets• Disease indications• Clinical progression• NHS prescription data3
Established targets Targets in trials
IN
DEVELOPMENT
Structure comparison resource8
• Intra-GPCR residue-residue interactions• Residue angles and properties• Compare interactions within or between sets of GPCR structures• Identify unique and conserved interaction patterns• Interactive visualization tools linked with a 3D protein viewer
• >30.000 mutagenesis data points• Mutant design tool
• Coupling data from Inoue et al., 2019, and Guide to Pharmacology
• Browse experimental data and constructs• Construct design tool• Thermostabilising mutation suggestions
Experiment Browser
Funding
NEW
ONLINE
• GPCR–G protein models• Based on newest structures
Web: www.GPCRdb.org
Email: [email protected]
@gpcrdb
Contact
Find these resources under the Signal Proteins menu option on gpcrdb.org
Arrest in and G prote in pages
Complex homology models
Coupl ing data Interact ion matr ix
• Find publication ready diagrams • Overlay with other data sources (PTM, Variants etc)
References5) Munk, C. et al. Nat Methods, 2019, 16, 151–162.
6) Hauser, A. S. et al. Cell, 2018, 172 (1-2), 41-54 e19.
7) Hauser, A. S. et al. Nat Rev Drug Discov, 2017, 16 (12), 829-842.
8) Access given upon request
