GPCR Workshop Agenda
Sheraton Waikiki, Honolulu, Hawaii December 7 - 10, 2010
The goal of this workshop is to explore ways to make structure-based drug discovery practical for G protein-coupled receptors. Most academic scientists with interests in GPCR structure, pharmacology and signaling have little experience in the practical aspects of structure-based drug discovery as is currently applied to soluble protein targets such as kinases and proteases. Similarly, scientists in the pharmaceutical industry with expertise in structure-based drug discovery (NMR spectroscopists, crystallographers, computational chemists) are often unaware of the possibilities and limitations of structural approaches to GPCRs. The goal of the workshop will be to facilitate communication between these two groups of scientists with the hope of fostering collaborations that will lead to more focused efforts to enable innovative approaches to structure-based drug discovery for GPCRs.
The format for this workshop will differ from more conventional conferences where scientists typically present a combination of previously published work and recently completed unpublished work. We would like to establish a format where there will be a free flow of ideas centered around the problems of structure-based drug discovery, and a discussion of what different investigators have tried, what has worked, and what has failed. The conference will follow the principles of the Gordon Research Conferences, where the participants will hold data and ideas discussed at the workshop in confidence.
We would like the format of the conference to be even more interactive than that commonly used by the GRC or Keystone conferences. Each session will have a panel of discussants who will give their perspective on elements of the topic (approximately 30 min with 10 min discussion), including relevant experimental data. The discussion will continue in the evening sessions where participants will have the opportunity to present a few slides of relevant data for discussion. Participants can request to present at the evening session either before or during the meeting. Discussion leaders will be responsible for selecting and organizing the material to be presented in the open forum. Posters will be encouraged. Evening discussion sessions may also include 20 min presentations selected from poster abstract
Anticipated outcome: To create a better understanding of problems faced and more focused approaches to resolve drug discovery problems; to establish long-term interactions between academics and industry; to convince funding agencies that basic research into GPCR structure will lead to therapeutic advances.
PROGRAM - SESSIONS AND TOPICS:
(speakers may be changed under special circumstances)
| Tuesday, December 7th | ||
| 2:00 – 4:00 PM | Registration | |
| 4:00 – 4:10 PM | Introduction to the meeting and format | Brian Kobilka, Stanford University, USA |
| Theme I | Challenges in drug discovery at GPCRs | Arthur Christopoulos, Chair |
| 4:10 – 4:50 PM | What kind of drug do you want? Efficacy and biased agonists | Robert Lefkowitz, Duke University, USA |
| 4:50 – 5:30 PM | Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation | Jonathan Javitch, Columbia University, USA |
| 5:30 – 5:50 PM | Break | |
| 5:50 – 6:30 PM | Structural and functional challenges for allosteric drug discovery | Arthur Christopoulos, Monash University, Australia |
| 6:30 – 7:10 PM | Screening strategies for identifying allosteric ligands | Robert Lütjens, Addex Pharma, Switzerland |
| 7:10 PM – | Free Time | |
| Wednesday, December 8th | ||
| Theme II | Chemical and informatic/computational issues in novel GPCR drug discovery | Patrick Sexton, Chair |
| 8:00 – 8:40 AM | Overview of current GPCR crystal structures – what have we learned? | Leonardo Pardo, Universitat Autonoma de Barcelona, Spain |
| 8:40 – 9:20 AM | Ab initio modeling of GPCRs | Patrick Sexton, Monash University, Australia |
| 9:20 – 10:00 AM | Homology modeling and ligand-directed modeling of GCPRs | Ruben Abagyan, University of California, San Diego, USA |
| 10:00 – 10:20 AM | Break | |
| 10:20 – 11:00 AM | GPCRs in motion: long-timescale molecular dynamic simulations | Ron Dror, D.E. Shaw Research, USA |
| 11:00 – 11:40 AM | Ligand docking and in silico screening | Brian Shoichet, University of California, San Francisco, USA |
| 11:40 – 12:20 PM | Computational approaches to improve the quality of structures obtained from weak diffraction data | Axel Brunger, Stanford University, USA |
| 12:20 – 2:30 PM | Break/Posters | |
| Theme IIIa | Structural Biology in Drug Discovery, part 1 GPCR structures | Masashi Miyano, Chair, Japan |
| 2:30 – 3:10 PM | Intramolecular signal transduction in Class C GPCRs | Jean Philippe Pin, Université Montpellier, France |
| 3:10 – 3:50 PM | Structural biology of Family B GPCR structures | Jonathan Moore, Vertex, USA |
| 3:50 – 4:30 PM | Active-state Family A GPCR structures | Gebhard Schertler, Paul Scherrer Institute, Switzerland |
| 4:30 – 7:00 PM | Free Time | |
| 7:00 – 10:00 PM | Interactive Discussion | Discussion leaders: Arthur Christopoulos and Masashi Miyano |
| Thursday, December 9th | ||
| Theme IIIb | Structural Biology in Drug Discovery, part 2 applications | Brian Kobilka, Chair |
| 8:00 – 8:40 AM | Application of X-ray crystallography in drug discovery for soluble protein targets | Andrew Tebben, Bristol Myers Squibb, USA |
| 8:40 – 9:20 AM | Outside the cytoplasm, biophysical ligand screening for membrane proteins | Gregg Siegal, University of Lieden, Netherlands |
| 9:20 – 10:00 AM | Application of Affinity Selection-Mass Spectrometry to GPCR drug discovery | Charles E Whitehurst, Merck, USA |
| 10:00 – 10:20 AM | Break | |
| 10:20 – 11:00 AM | Probing ligand dependent conformations and conformational dynamics of the ß₂AR by 19F NMR. | Scott Prosser, University of Toronto, Canada |
| 11:00 – 11:40 AM | Insights into the structure and activation of rhodopsin by NMR spectroscopy | Steven O. Smith, Stony Brook University, USA |
| 11:40 – 2:00 PM | Break / Posters | |
| Theme IV (part 1) | Making GPCR structural biology more tractable – technical challenges | Roger Sunahara, Chair |
| 2:00 – 2:40 PM | Conformational thermostabilization of GPCRs to facilitate structure determination | Chris Tate, Laboratory of Molecular Biology, MRC Cambridge, UK |
| 2:40 – 3:20 PM | Bacterial expression and refolding of GPCRs | Jean-Louis Bančres, Université Montpellier, France |
| 3:20 – 3:40 PM | Break | |
| 3:40 – 4:20 PM | A GFP-based platform for rapid construction and evaluation of highly expressed and stable GPCR variants in Saccharomyces cerevisiae | Takuya Kobayashi, Kyoto University, Japan |
| 4:20 – 5:00 PM | G proteins as selective conformational filters on GPCRs | Roger Sunahara,University of Michigan, USA |
| 5:30 – 7:30 PM | Interactive Discussion | Discussion leaders: Roger Sunahara and Brian Kobilka |
| 8:00 PM – | Banquet | |
| Friday, December 10th | ||
| Theme IV (part 2) | Making GPCR structural biology more tractable – technical challenges | Brian Kobilka, Chair |
| 9:00 – 9:40 AM | Structural basis of M3 muscarinic receptor dimer/oligomer formation | Jürgen Wess, NIDDK, NIH, USA |
| 9:40 – 10:20 AM | Novel detergents for stabilizing GPCRs | Pil Seok Chae, University of Wisconsin, and Sřren Rasmussen, Stanford University, USA |
| 10:20 – 10:40 AM | Break | |
| 10:40 – 11:20 AM | Xaperone assisted X-ray crystallography: conformation selective Nanobodies to solve active state GPCR structures | Jan Steyaert, Free University of Brussels, Belgium |
| 11:20 – 12:00 PM | Discussion | |