Web Desc
Structure Based Drug Discovery
Organizer(s): Stephen K. Burley, Brian K. Shoichet and Paul A. Bartlett
Date: April 04 - 09, 2006
Location: Fairmont Chateau Whistler, Whistler, BC, Canada
Sponsored by Chiron Corporation
Summary of Meeting:
This conference will focus on several exciting new developments in Structure Based Drug Discovery, including: fragment based lead discovery/lead optimization, high-throughput X-ray and NMR structure determination of protein ligand complexes, computational analyses of ligand-receptor interactions and prediction of novel ligands, ligand binding selectivity, and ADME/toxicity properties. Major/pivotal problems facing both academic and industrial scientists include the following: (a) understanding precisely what constitutes a good starting point for lead optimization (b) understanding how best to optimize selectivity and avoid problems with ADME/toxicity (c) understanding the limitations of currently available in silico methods (d) understanding how to combine the results of biophysical characterization of protein-ligand interactions with medicinal chemistry to produce potent/selective lead compounds and (e) developing sufficient expertise/experience to bring membrane proteins and macromolecular interactions within the purview of structure based drug discovery. Upon completion of this conference, participants should: - Appreciate the challenges represented by membrane proteins and macromolecular interactions as targets for structure based drug discovery. - Understand current approaches to fragment based drug discovery. - Appreciate the state-of-the-art in automated approaches to determination of protein-ligand complex structures with solution NMR spectroscopy and X-ray crystallography. - Understand the roles that homology modeling and computational docking play in structure based drug discovery. - Appreciate the contributions that structural studies can make to lead optimization and our understanding of selectivity and ADME/Toxicity. - Understand the limitations of current in silico methods for de novo drug discovery.
Scholarship Deadline: December 5 2005
Discounted Abstract Deadline: December 5 2005
Abstract Deadline: December 28 2005
Discounted Registration Deadline: February 3 2006
We gratefully acknowledge additional support for this conference from:
Chiron CorporationFisher Scientific, Global Chemicals Division
ISOTEC, a member of the Sigma-Aldrich Group
Novartis Institutes for BioMedical ResearchRoyal Society of ChemistryVarian, Inc.
We gratefully acknowledge additional in-kind support for this conference from those foregoing speaker expense reimbursements:

GlaxoSmithKline Research & Development, Ltd.

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Merck Research Laboratories

Novartis Institutes for BioMedical Research

Pfizer Inc.

Roche Palo Alto

SGX Pharmaceuticals

Sunesis Pharmaceuticals, Inc.
We gratefully acknowledge the generous grant for this conference provided by:

National Institute of General Medical Sciences (NIGMS)
Grant No. 1R13 GM076892-01
We appreciate the organizations that provide Keystone Symposia with additional support, such as marketing and advertising:

Click here to view more of these organizations
Special thanks to the following for their support of Keystone Symposia initiatives to increase participation at this meeting by scientists from underrepresented backgrounds:

Click here to view more of these organizations

Program

Tuesday, April 04 | 3:00PM - 7:30PM
Registration
Room: MacDonald Foyer


Tuesday, April 04 | 6:30PM - 7:30PM
Refreshments
Room: MacDonald Foyer


Tuesday, April 04 | 7:30PM - 8:30PM
Keynote Session: Perspectives on Structure-Based Drug Discov
ery
Room: MacDonald AB

Speaker 1 of 2
* Stephen K. Burley, Rutgers University, USA

Tuesday, April 04 | 7:30PM - 8:30PM
Keynote Session: Perspectives on Structure-Based Drug Discov
ery
Room: MacDonald AB

Speaker 2 of 2
Wayne A. Hendrickson, Columbia University, USA
Past, Present and Future

Wednesday, April 05 | 7:00AM - 8:00AM
Breakfast
Room: MacDonald CD


Wednesday, April 05 | 8:00AM - 11:15AM
Modeling Protein-Ligand Interactions
Room: MacDonald AB

Speaker 1 of 7
* Kenneth M. Merz, Jr., University of Florida, USA

Wednesday, April 05 | 8:00AM - 11:15AM
Modeling Protein-Ligand Interactions
Room: MacDonald AB

Speaker 2 of 7
Charles L. Brooks III, The Scripps Research Institute, USA
Modeling the Influence of Solvation in Ligand Binding

Wednesday, April 05 | 8:00AM - 11:15AM
Modeling Protein-Ligand Interactions
Room: MacDonald AB

Speaker 3 of 7
Bruce Tidor, Massachusetts Institute of Technology, USA
Role of Electrostatics in Ligand Binding and Design

Wednesday, April 05 | 8:00AM - 11:15AM
Modeling Protein-Ligand Interactions
Room: MacDonald AB

Speaker 4 of 7
Bertrand E. Garcia-Moreno, Johns Hopkins University, USA
Electrostatic effects in the protein interior

Wednesday, April 05 | 8:00AM - 11:15AM
Modeling Protein-Ligand Interactions
Room: MacDonald AB

Speaker 5 of 7
Michael K. Gilson, University of California, San Diego, USA
Theory and Modeling of Molecular Recognition

Wednesday, April 05 | 8:00AM - 11:15AM
Modeling Protein-Ligand Interactions
Room: MacDonald AB

Speaker 6 of 7
Sandor Vajda, Boston University, USA
Short Talk: Computational Mapping of Proteins for Fragment Based Drug Design

Wednesday, April 05 | 8:00AM - 11:15AM
Modeling Protein-Ligand Interactions
Room: MacDonald AB

Speaker 7 of 7
Richard David Cramer, Tripos Inc., USA
Short Talk: Should Ligand Structures be Physically Correct or Statistically
Comparable?


Wednesday, April 05 | 9:20AM - 9:40AM
Coffee Break
Room: MacDonald Foyer


Wednesday, April 05 | 11:15AM - 1:00PM
Poster Setup
Room: MacDonald CD


Wednesday, April 05 | 1:00PM - 10:00PM
Poster Viewing
Room: MacDonald CD


Wednesday, April 05 | 4:30PM - 5:00PM
Coffee Available
Room: MacDonald Foyer


Wednesday, April 05 | 5:00PM - 7:15PM
High-Throughput Elucidation of Structural Information
Room: MacDonald AB

Speaker 1 of 5
Andrzej Joachimiak, Argonne National Laboratory, USA
Ultra-High Resolution X-ray Structure DetermInation at the Advanced Photon Source

Wednesday, April 05 | 5:00PM - 7:15PM
High-Throughput Elucidation of Structural Information
Room: MacDonald AB

Speaker 2 of 5
David Cowburn, Albert Einstein College of Medicine, USA
Structure Based Drug Discovery and High-Field NMR Spectroscopy

Wednesday, April 05 | 5:00PM - 7:15PM
High-Throughput Elucidation of Structural Information
Room: MacDonald AB

Speaker 3 of 5
Aled M. Edwards, University of Toronto, Canada
Structural Chemistry of Human Protein Families

Wednesday, April 05 | 5:00PM - 7:15PM
High-Throughput Elucidation of Structural Information
Room: MacDonald AB

Speaker 4 of 5
Paul C. Driscoll, MRC-National Institute for Medical Research, UK
Short Talk: Combinatorial Domain Hunting – A High Throughput Approach to Identification of Soluble Protein Constructs

Wednesday, April 05 | 5:00PM - 7:15PM
High-Throughput Elucidation of Structural Information
Room: MacDonald AB

Speaker 5 of 5
Andrew May, Sana Biotechnology, Inc., USA
Short Talk: Parallelization of Macromolecular Crystallization using Microfluidic Free-Interface Diffusion

Wednesday, April 05 | 7:15PM - 8:15PM
Social Hour with Lite Bites
Room: MacDonald CD


Wednesday, April 05 | 7:30PM - 10:00PM
Poster Session 1
Room: MacDonald CD


Thursday, April 06 | 7:00AM - 8:00AM
Breakfast
Room: MacDonald CD


Thursday, April 06 | 8:00AM - 11:15AM
Fragment-Based Lead Generation
Room: MacDonald AB

Speaker 1 of 7
* Stephen K. Burley, Rutgers University, USA

Thursday, April 06 | 8:00AM - 11:15AM
Fragment-Based Lead Generation
Room: MacDonald AB

Speaker 2 of 7
Tom L. Blundell, University of Cambridge, UK
Structural Biology and Cancer: Fragment Based Approaches to Drug Discovery

Thursday, April 06 | 8:00AM - 11:15AM
Fragment-Based Lead Generation
Room: MacDonald AB

Speaker 3 of 7
Jeff Blaney, Genentech, Inc., USA
FAST Lead Discovery

Thursday, April 06 | 8:00AM - 11:15AM
Fragment-Based Lead Generation
Room: MacDonald AB

Speaker 4 of 7
Jeffrey S. Wiseman, Locus Pharmaceuticals, USA
Successes with Purely Computational Fragment-Based Drug Design

Thursday, April 06 | 8:00AM - 11:15AM
Fragment-Based Lead Generation
Room: MacDonald AB

Speaker 5 of 7
Dean R. Artis, Elan, USA
Applications of Scaffold-Based Drug Discovery to Targets in Oncology and Metabolic Disease

Thursday, April 06 | 8:00AM - 11:15AM
Fragment-Based Lead Generation
Room: MacDonald AB

Speaker 6 of 7
Jörg Degen, 4SC AG, Germany
Short Talk: FlexNovo: Structure-Based Searching in Large Fragment Spaces

Thursday, April 06 | 8:00AM - 11:15AM
Fragment-Based Lead Generation
Room: MacDonald AB

Speaker 7 of 7
Désirée H. Tsao, Wyeth Pharmaceuticals, USA
Short Talk: NMR Based Approaches in the Study of Protein/Ligand Interactions: Drug Discovery at Wyeth Research

Thursday, April 06 | 9:20AM - 9:40AM
Coffee Break
Room: MacDonald Foyer


Thursday, April 06 | 11:00AM - 1:00PM
Poster Setup
Room: MacDonald CD


Thursday, April 06 | 1:00PM - 10:00PM
Poster Viewing
Room: MacDonald CD


Thursday, April 06 | 4:30PM - 5:00PM
Coffee Available
Room: MacDonald Foyer


Thursday, April 06 | 5:00PM - 7:15PM
Understanding Ligand Binding Specificity
Room: MacDonald AB

Speaker 1 of 6
* Paul A. Bartlett, University of California, Berkeley, USA

Thursday, April 06 | 5:00PM - 7:15PM
Understanding Ligand Binding Specificity
Room: MacDonald AB

Speaker 2 of 6
Louise N. Johnson, University of Oxford, UK
Protein kinase substrate recognition

Thursday, April 06 | 5:00PM - 7:15PM
Understanding Ligand Binding Specificity
Room: MacDonald AB

Speaker 3 of 6
Kevan M. Shokat, University of California, San Francisco, USA
PI3K Target Validation in Glioma Using a Matrix of Selective Small Molecule PI3K Inhibitors

Thursday, April 06 | 5:00PM - 7:15PM
Understanding Ligand Binding Specificity
Room: MacDonald AB

Speaker 4 of 6
Christopher Whitehead, Pfizer Inc., USA
Allosteric Inhibitors Provide Selectivity for Protein Kinases

Thursday, April 06 | 5:00PM - 7:15PM
Understanding Ligand Binding Specificity
Room: MacDonald AB

Speaker 5 of 6
Kunbin Qu, OncoMed, USA
Short Talk: Target Janus Kinase 3 to Prevent Transplantation Rejection

Thursday, April 06 | 5:00PM - 7:15PM
Understanding Ligand Binding Specificity
Room: MacDonald AB

Speaker 6 of 6
William M. Rockey, University of Iowa, USA
Short Talk: Rapid Computational Identification of the Targets of Protein Kinase Inhibitors

Thursday, April 06 | 7:15PM - 8:15PM
Social Hour with Lite Bites
Room: MacDonald CD


Thursday, April 06 | 7:30PM - 10:00PM
Poster Session 2
Room: MacDonald CD


Friday, April 07 | 7:00AM - 8:00AM
Breakfast
Room: MacDonald CD


Friday, April 07 | 8:00AM - 11:15AM
Lead Optimization: Selectivity and ADME/Toxicity
Room: MacDonald AB

Speaker 1 of 6
Michael Hann, GlaxoSmithKline Medicines Research Centre, UK
Lead-Like Properties: Creating Space for Effective Lead Optimisation?

Friday, April 07 | 8:00AM - 11:15AM
Lead Optimization: Selectivity and ADME/Toxicity
Room: MacDonald AB

Speaker 2 of 6
Tudor I. Oprea, University of New Mexico School of Medicine, USA
Clinical Pharmacokinetics Models in Lead Discovery

Friday, April 07 | 8:00AM - 11:15AM
Lead Optimization: Selectivity and ADME/Toxicity
Room: MacDonald AB

Speaker 3 of 6
Michael C. Sanguinetti, University of Utah, USA
A Site-Directed Mutagenesis Approach to Define Drug Binding Sites on hERG

Friday, April 07 | 8:00AM - 11:15AM
Lead Optimization: Selectivity and ADME/Toxicity
Room: MacDonald AB

Speaker 4 of 6
* John W. Kozarich, ActivX Biosciences, Inc., USA
A Chemo-Proteomic Approach for Interrogating Nucleotide-Binding Space and Assessing Drug Selectivity/Toxicity

Friday, April 07 | 8:00AM - 11:15AM
Lead Optimization: Selectivity and ADME/Toxicity
Room: MacDonald AB

Speaker 5 of 6
Charles J. Eyermann, University of Cape Town, South Africa
Short Talk: Structure-Guided Optimization of Pyrazolopyrimidinediones as Agents Specific for Treating Helicobacter pylori Infections

Friday, April 07 | 8:00AM - 11:15AM
Lead Optimization: Selectivity and ADME/Toxicity
Room: MacDonald AB

Speaker 6 of 6
Colin W. G. Fishwick, University of Leeds, UK
Short Talk: De Novo Computational Design, Synthesis, and Biological Evaluation of New Inhibitors of Early-Stage Bacterial Peptidoglycan Biosynthesis Enzymes

Friday, April 07 | 9:20AM - 9:40AM
Coffee Break
Room: MacDonald Foyer


Friday, April 07 | 4:30PM - 5:00PM
Coffee Available
Room: MacDonald Foyer


Friday, April 07 | 5:00PM - 7:00PM
Docking to Experimental Structures and Homology Models
Room: MacDonald AB

Speaker 1 of 4
* Brian K. Shoichet, University of California, San Francisco, USA
Understanding Hits and Decoys in Molecular Docking

Friday, April 07 | 5:00PM - 7:00PM
Docking to Experimental Structures and Homology Models
Room: MacDonald AB

Speaker 2 of 4
Leslie A. Kuhn, Michigan State University, USA
Multiscale Modeling of Protein and Ligand Flexibility Applied to Screening for Novel Inhibitors

Friday, April 07 | 5:00PM - 7:00PM
Docking to Experimental Structures and Homology Models
Room: MacDonald AB

Speaker 3 of 4
Gerhard Klebe, Philipps University Marburg, Germany
Virtual Screening for Protein Targets Defined To Decreasing Structural Accuracy


Friday, April 07 | 5:00PM - 7:00PM
Docking to Experimental Structures and Homology Models
Room: MacDonald AB

Speaker 4 of 4
Paul C. Hawkins, Openeye Scientific Software, USA
Short Talk: Shape-Based Methods in Virtual Screening: A Superior Choice to Docking?

Friday, April 07 | 7:00PM - 8:00PM
Social Hour with Lite Bites
Room: MacDonald CD


Saturday, April 08 | 7:00AM - 8:00AM
Breakfast
Room: MacDonald CD


Saturday, April 08 | 8:00AM - 11:15AM
Case Studies in Structure-Based Drug Discovery
Room: MacDonald AB

Speaker 1 of 7
* Charles H. Reynolds, USA

Saturday, April 08 | 8:00AM - 11:15AM
Case Studies in Structure-Based Drug Discovery
Room: MacDonald AB

Speaker 2 of 7
Michelle F. Browner, Johnson & Johnson Innovation, USA
HCV Polymerase Drug Discovery: Multiple Opportunities and Challenges

Saturday, April 08 | 8:00AM - 11:15AM
Case Studies in Structure-Based Drug Discovery
Room: MacDonald AB

Speaker 3 of 7
Siegfried H. Reich, Eli Lilly, USA
'Application of Structure-Based Design to Facilitate the Identification of Clinical Candidates: Some Examples'

Saturday, April 08 | 8:00AM - 11:15AM
Case Studies in Structure-Based Drug Discovery
Room: MacDonald AB

Speaker 4 of 7
Ralph Mosley, Pharmasset, Inc., USA
PPARs-Modeling, Structure and Mutagenesis: A True Story

Saturday, April 08 | 8:00AM - 11:15AM
Case Studies in Structure-Based Drug Discovery
Room: MacDonald AB

Speaker 5 of 7
Michelle R. Arkin, Sunesis Pharmaceutical, USA
Drug Discovery at Hormone-Receptor Interfaces: Two Case Studies

Saturday, April 08 | 8:00AM - 11:15AM
Case Studies in Structure-Based Drug Discovery
Room: MacDonald AB

Speaker 6 of 7
S. Donald Emerson, Pfizer Inc., USA
Short Talk: NMR Auxiliary Binding Screen for Lead Optimization: Design of Novel Renin Inhibitors that Access the S2 Pocket

Saturday, April 08 | 8:00AM - 11:15AM
Case Studies in Structure-Based Drug Discovery
Room: MacDonald AB

Speaker 7 of 7
Max Cummings, Janssen R&D, USA
Short Talk: Small Molecule Inhibitors of Protein-Protein Interactions

Saturday, April 08 | 9:20AM - 9:40AM
Coffee Break
Room: MacDonald Foyer


Saturday, April 08 | 4:30PM - 5:00PM
Coffee Available
Room: MacDonald Foyer


Saturday, April 08 | 5:00PM - 7:15PM
Inhibiting Macromolecular Interactions
Room: MacDonald AB

Speaker 1 of 5
* Christopher D. Lima, Memorial Sloan Kettering Cancer Center, USA
The SUMO Pathway: Insights into Ubiquitin and Ubiquitin-Like Protein Conjugation

Saturday, April 08 | 5:00PM - 7:15PM
Inhibiting Macromolecular Interactions
Room: MacDonald AB

Speaker 2 of 5
Axel T. Brunger, Stanford University, USA
Botulinum Neurotoxin - SNARE Interactions

Saturday, April 08 | 5:00PM - 7:15PM
Inhibiting Macromolecular Interactions
Room: MacDonald AB

Speaker 3 of 5
Christopher Straub, Novartis Institutes for BioMedical Research, USA
Inhibitors of Apoptosis Proteins: Using Structure Based Drug Design to Tame a Protein-Protein Interaction Target

Saturday, April 08 | 5:00PM - 7:15PM
Inhibiting Macromolecular Interactions
Room: MacDonald AB

Speaker 4 of 5
Trina L. Foster, Duke University, USA
Short Talk: Peptide and Peptidomimetic Inhibition of Protein-Protein Interactions: Developing New Therapeutics for Old Targets

Saturday, April 08 | 5:00PM - 7:15PM
Inhibiting Macromolecular Interactions
Room: MacDonald AB

Speaker 5 of 5
Alain Boudreault, Aegera Therapeutics Inc., Canada
Short Talk: XIAP BIR Binding Small Molecule Inhibitors Lead to Highly Active Pro-Apoptotic Compounds in Cancer Cell Lines

Saturday, April 08 | 7:15PM - 8:15PM
Social Hour with Lite Bites
Room: MacDonald CD


Saturday, April 08 | 8:00PM - 11:00PM
Entertainment
Room: MacDonald CD


Saturday, April 08 | 8:15PM - 11:00PM
Cash Bar
Room: MacDonald CD


Sunday, April 09 | 10:26AM - 10:26AM
Departure


*Session Chair.