Structure-Based Drug Design Conference Final Brochure.pdf

Final Agenda
Cambridge Healthtech Institute and Bio-IT World Present the Eleventh Annual
Structure-Based
Drug Design
Rational
June 8-10, 2011 • Royal Sonesta Hotel Boston • Cambridge, MA
Molecular
Approaches to Targeted
Therapeutics — From
Fragments to Biology
Register by
March 11, 2011
and Save
up to $350!
Conference Highlights:
• Protein Flexibility
• Fully Synthetic
Protein-Protein
Interaction Inhibitor
• Fragment-to-Lead
Optimization
• High Performance
Computing and
Collaborative Drug Design
• State-of-the-Art Molecular
Dynamics Simulations
healthtech.com/SBD
Keynote Speaker:
Millisecond-Long Molecular
Dynamics Simulations of Proteins
on a Special-Purpose Machine
David E. Shaw, Ph.D.,
Chief Scientist,
D. E. Shaw Research
Dinner Short Course:
June 8, 2011
Identification of Druggable Sites for
Protein-Protein Interaction Targets
Co-Located with:
Next-Gen Kinase Inhibitors:
Across Multiple Therapeutic Areas
June 6-8, 2011
healthtech.com/KIN
Corporate Sponsors:
Corporate Support
Sponsors:
Official
Publication:
Organized by:
Cambridge Healthtech Institute

WEDNESDAY, JUNE 8
12:00-1:20 pm Main Conference Registration
STRUCTURE-BASED KINASE INHIBITOR DESIGN
& KINASE SELECTIVITY
(Shared session with Next-Gen Kinase Inhibitors Conference)
1:10 Chairperson’s Remarks
Andrew C. Good, Ph.D., Distinguished Scientific Fellow, Medicinal
Chemistry, Genzyme Corp.
1:15 Discovery of Crizotinib (PF-02341066)-A c-Met/ALK Dual
Inhibitor for Oncology Applications
Jean Cui, Ph.D., Associate Research Fellow, Oncology Medicinal
Chemistry, Pfizer, Inc.
Crizotinib (PF-02341066) has shown remarkable efficacy for lung cancer
patients with EML4-ALK fusion gene and is currently in Phase III clinical
trials. Crizotinib is created as a c-Met/ALk dual inhibitor using structurebased
drug design in combination with medicinal chemistry principles.
1:45 A Role for Hydration in Interleukin-2 Inducible T Cell
Kinase Selectivity
Ronald Knegtel, Ph.D., Research Fellow I, Molecular Modeling, Vertex
Pharmaceuticals (Europe) Ltd.
A series of Itk inhibitors that achieve selectivity through the introduction
of a single, solvent exposed aromatic nitrogen atom without direct
interactions with the enzyme is reported. By analyzing active site
hydration using WaterMap, the selectivity profile can be explained in
terms of the replacement of a thermodynamically unfavorable water
molecule by the inhibitor and improved hydration of the bound ligand.
This hydration site was successfully used to enrich virtual screening
results in their content of selective Itk inhibitors.
2:15 Overcoming Drug-Resistant Mutations in Kinase Drug
Discovery: Applying Lessons from Ponatinib (AP24534)
David C. Dalgarno, Ph.D.,Vice President, Research
Technologies, ARIAD Pharmaceuticals, Inc.
Ponatinib (AP24534) is a novel BCR-ABL inhibitor that
inhibits both native and mutant BCR-ABL, including the
T315I gatekeeper mutation, and hence acts as a pan-BCR-
ABL inhibitor. We recently analyzed the structural basis for
this pan-BCR-ABL activity. Here we discuss this analysis and how it can
be applied to other kinase targets exhibiting mutation-based resistance,
and how the lessons from ponatinib can be applied to the design of
other mutant kinase inhibitors.
2:45 Structure-Based Kinase Sponsored by
Inhibitor Design & Kinase Selectivity
Stephen A. Parent, Ph.D., Director of Business
Development, Reaction Biology Corporation
RBC provides drug profiling and screening services using HotSpot
technology, a high-throughput radioisotopic screening platform with
more than 370 kinases. We will describe its application to kinase
inhibitor development and kinase inhibitor selectivity.
3:00 Networking Refreshment Break in the Exhibit Hall with
Poster Viewing
3:30 Structure-Guided Fragment-Based Drug Discovery for
Protein Kinase Targets
Stephen K. Burley, M.D., D.Phil., Distinguished Lilly Research
Scholar, Lilly Biotechnology Center, Eli Lilly and Company
4:00 How Molecular Dynamics Simulation May be Applied in
Structural Based Design of Kinase Drugs
Yibing Shan, Ph.D., Senior Scientist, Chemistry and Biology, D. E. Shaw
Research
The understanding of the extensive conformational heterogeneity of
protein kinases is crucial to the understanding of kinase drugs’ binding
and specificity. To this end, long molecular dynamics (MD) simulations,
which for the first time reached the relevant timescale of micro- to millisecond,
may prove a powerful tool. Our MD study of Abl, Src, and EGFR
kinases will be discussed as examples of such effort in its early stage.
4:30 Recent experience establishing a new lead ID capability
to pursue oncology kinase targets.
Hans-Peter Biemann, Ph.D., Associate Scientific Director, In vitro Biology,
Genzyme Corporation
Genzyme’s small molecule discovery unit has incorporated fragmentbased
and x-ray structure-assisted technologies over the last three
years. Ligands of 150-250 Daltons have undergone structure-assisted
elaboration to identify novel potent and selective inhibitors of tyrosine
and ser/thr kinases, including Pim-1. One program progressed a
tyrosine kinase to late lead optimization in 2.5 years and newer projects
have productively commenced outside of the kinase and oncology
sectors. This evolution of our HTS-based drug discovery unit to a multiplatform
format enables us to address a number of target classes more
expediently than before.
5:00 Longstanding Kinase Contributor Panel: Structure-Based
Kinase Inhibitor Design
Topic: Insights correlating kinase selectivity and toxicity
Andrew C. Good, Ph.D., Distinguished Scientific Fellow, Medicinal
Chemistry, Genzyme Corp.
Ravi G. Kurumbail, Ph.D., Research Fellow and Structural Biology
Laboratory Head, Pfizer, Inc.
Dirksen Bussiere, Ph.D., M.B.A., Director, Structural Chemistry, Novartis
Institutes for BioMedical Research
5:00-6:00 Registration for Dinner Short Course
Wednesday Evening, June 8, 2011
Dinner Short Course*
6:00-9:00 pm Identification of Druggable Sites for Protein-
Protein Interaction Targets
Despite the growing number of examples of small molecule
inhibitors that disrupt protein-protein interactions (PPIs), the
origin of druggability is poorly understood. This course is
designed to demonstrate the use of computational methods
to determine the most likely structure of the complex formed
by interacting proteins, identify potentially druggable sites in
the interface, determine whether the target is druggable, and
provide information on potential ligands. Participants will study a
number of targets using web-based software (including PIPER and
ClusPro, currently the best protein docking tools available) on their
laptops.
Course Instructors:
Dima Kozakov, Ph.D., Research Assistant Professor, Departments of
Biomedical Engineering, Boston University
Dmitry Beglov, Ph.D., Senior Research Scientist, Structural
Bioinformatics Laboratory, Boston University
Ryan Brenke, Ph.D., Postdoctoral Research Associate,
Structural Bioinformatics Laboratory and Department of Chemistry,
Boston University
David R. Hall, Ph.D. student, Department of Biomedical Engineering,
Boston University
*Separate Registration Required
THURSDAY, JUNE 9
8:00 am Morning Coffee
PROTEIN FLEXIBILITY AND DRUGGABILITY
8:25 Chairperson’s Opening Remarks
Woody Sherman, Ph.D., Vice President, Applications Science,
Schrodinger, Inc.
8:30 FAST Prediction of Protein Stability and Flexibility
Donald Jacobs, Ph.D., Associate Professor of Physics,
Physics and Optical Science, University of North Carolina
Funded by NIH R01-GM073082, a novel computational
method based on free energy decomposition and an iterative
self-consistent reconstitution involving network rigidity to
account for non-additivity in conformational entropy due to
correlated motions has been developed. The program, FAST, provides a
Flexibility And Stability Test for proteins that quantifies stability/flexibility
relationships for understanding function. Speed versus accuracy is
optimized for high-throughput screening to test for structure/function
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elationships in mutation studies, substrate binding, pKa predictions,
allostery, protein-protein interactions and protein formulation.
8:55 Predicting Selectivity and Druggability in Small Molecule
Drug Discovery
Alan Cheng, Ph.D., Senior Scientist, Chemistry Research &
Development, Amgen, Inc.
Structure-based druggability and selectivity analyses
increasingly inform target assessment and setting of lead
optimization strategies in drug discovery. Continuing work
on druggability prediction will be presented in the context of
applying druggability prediction approaches to large numbers of protein
structures. Work on selectivity analysis will be presented in the context
of kinase inhibitor discovery examples from Amgen, and we will show
how a thermodynamics-based selectivity index can help in predicting
biological selectivity.
9:20 Development of a Simple Metric for the Structure-Based
Assessment of Protein Druggability
Emanuele Perola, Ph.D., Research Fellow I, Vertex
Pharmaceuticals
Accurate assessments of target druggability could
significantly reduce the attrition rate in drug discovery
programs. We developed an algorithm to isolate and
characterize the binding pockets of protein targets and
used it to analyze a set of validated drug targets and a diverse set of
proteins with known crystal structures. We identified five parameters
that differentiate the two sets in a statistically significant manner and
derived a set of simple rules that could be applied to estimate the
druggability of prospective targets.
9:45 Improvements in Predicting Sponsored by
Protein-Ligand Binding Energies: Waters,
Protein Flexibility, and Empirical Scoring
Woody Sherman, Ph.D., Vice President, Applications Science,
Schrodinger, Inc.
Recent years have seen significant advancements in
structure-based drug design methods. The inclusion of
explicit waters and protein flexibility have proven to be
critical components of improved protein-ligand scoring. We
will discuss these advances and how they have produced more robust
scoring and have been integrated into the Glide XP empirical scoring
function to significantly improve virtual screening enrichments.
10:15 Networking Coffee Break in the Exhibit Hall with Poster
Viewing
PROTEIN-PROTEIN INTERACTION
10:45 Identification of Druggable Sites for Protein-Protein
Interaction Targets by Computational Fragment Mapping
Dima Kozakov, Ph.D., Research Assistant Professor, Departments of
Biomedical Engineering, Boston University
We have developed computational fragment mapping to identify “hot
spot” regions in protein-protein interfaces. The method accounts for
protein plasticity, and finds energetically favorable sites for fragment
sized probe molecules. Results are presented for protein-protein
interaction targets, including interleukin-2, Bcl-xL, MDM2, HPV-11 E2,
ZipA, TNF-a, NEMO, and eIF4E. We also discuss methods of finding
druggable targets in cancer pathways.
11:10 Induced Fit Modeling with Monte Carlo Techniques:
Protein Energy Landscape Exploration
Victor Guallar, Ph.D., ICREA Research Professor, Life Science
Department, Barcelona Supercomputing
Protein energy landscape exploration (PELE) constitutes a
remarkable advance over conventional techniques to map
protein and protein-ligand dynamics. This method, which
combines protein structure prediction techniques with
a metropolis algorithm, is capable of describing the all-atom ligand
migration pathway and induced fit in approximately 100 hours of CPU.
A more recent developments in protein-ligand and protein-protein
induced fit will be presented.
11:35 Antagonizing the IAP proteins to Induce Programmed
Cell Death in Cancer: A New Therapeutic Approach Utilizing
Protein-Protein Interaction
Kurt Deshayes, Ph.D., Senior Scientist, Department of Early
Discovery Biochemistry, Genentech, Inc.
Inhibitor of apoptosis (IAP) proteins are expressed at
elevated levels in human malignancies and block cell
death in response to diverse stimuli. They are targets for
small molecule cancer therapeutics under current clinical
development. Results from biophysical, chemical, and molecular
biological studies of the mechanism by which binding of small molecule
IAP antagonists leads to cancer cell death will be reported.
12:00 pm Target based lead optimization: Sponsored by
VLifeSCOPE and SATREA
Sudhir A. Kulkarni, Ph.D., Vice President, Discovery
Research, VLife Sciences Technologies Pvt. Ltd.
VLifeSCOPE is a novel target based lead optimization method where
target ligand interactions obtained from scoring function are partitioned
into individual residues in the active site and correlated to the activity
of molecules. VLifeSCOPE provides information on key residues to
be targeted in lead optimization. SATREA is a visualization tool that
provides information on regions of exploitation and avoidance for
achieving specificity of target of interest with respect to other target in
the same family.
12:30 Luncheon Presentations (Sponsorship Opportunities
Available) or Lunch on Your Own
FRAGMENT-BASED DRUG DESIGN
1:30 Chairperson’s Remarks
Roderick Hubbard, Ph.D., Professor, University of York and Vernalis Ltd.
1:35 Practical Concepts in Fragment-to-Lead Optimization
Marcel Verdonk, Ph.D., Director, Computational Chemistry and
Informatics, Astex Therapeutics Ltd.
Fragment-based screening methodologies have become widely used
in drug discovery projects. We will present various practical concepts
that are used at Astex during the process of fragment prioritization and
optimizations. For example, we will discuss the use of Ligand Efficiency
and Group Efficiency measures. In addition, a practical approach will
be presented to significantly improve docking performance during
fragment-to-lead optimization
2:00 Making Decisions in Fragment-Based Discovery
Roderick Hubbard, Ph.D., Professor, University of York and
Director, Stuctural Sciences, Vernalis Ltd.
Fragment-based methods are now well established and
generate hits for most targets. A continuing challenge is
making the right decisions during the fragment to lead
evolution stage – which fragment to evolve based on
chemical and target opportunities and how to evolve fragments in the
absence of structure. This presentation will discuss the contribution
of both computational and experimental methods to address these
challenges.
2:30 Applying Integral Equation Sponsored by
Theory to Structure Based Design
Jean-François Truchon, Ph.D., Research Scientist,
Chemical Computing Group
Integral equation theories seem attractive for their ability to generate
water and solvated fragment density distributions in enzyme active
sites. They are much less computationally demanding than Molecular
Dynamics and unveil explicit solvent details missing in continuum
models such as Poisson-Boltzmann. We compare a particular flavor,
namely 3D-RISM/KH, to other methods and examine its usefulness in
structure based design and fragment docking.
3:00 Networking Refreshment Break in the Exhibit Hall with
Poster Viewing
3:45 A Computational Approach to Fragment-Based Drug Design
Charles H. Reynolds, Ph.D., Senior Director, Discovery
Technologies, Ansaris
We have developed a free energy method for computing
the interaction of small molecule fragments with their
target proteins. This approach is fast relative to traditional
free energy methods and more accurate than traditional
modeling methods that only compute interaction energies based on
one, or a small number, of configurations. The methodology is ideal for
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characterizing critical waters (e.g. tight-binding), assessing the affinities
of small molecule fragments, and identifying hot spots in proteinprotein
interaction targets.
4:10 Next-Generation Shape Signatures: A Powerful Tool for
Fragment-Based Drug Discovery
Randy Zauhar, Ph.D., Associate Professor, Chemistry & Biochemistry,
University of the Sciences
The original Shape Signatures method uses a ray-tracing approach to
efficiently explore the volume and surface properties of a molecule.
In our new approach, molecules are automatically partitioned into
fragments, and the Shape Signatures descriptors are now likewise
fragment-based. Query and target molecules are now compared by
matching fragment in all ways compatible with the underlying structure.
4:35 Panel Discussions:
Topic: What are the challenges and opportunities for the next
stages of development in fragment-based methods
For many targets, the identification of fragments that bind is for
the most part a solved problem. There are two main issues for the
methods. The first is deciding which fragments to take forward – there
can be hit rates of 5-10% for some targets. The second is how to guide
the early stages of chemical optimisation in the absence of crystal
structures, which is a particular problem for challenging targets such
as protein-protein interactions. The discussion will ask for opinions
on how computational methods could tackle these issues and what
developments are still needed.
5:00 Networking Cocktail Reception in the Exhibit Hall with
Poster Viewing
6:00 End of Day
FRIDAY, JUNE 10
HIGH PERFORMANCE COMPUTING AND
COLLABORATIVE DRUG DESIGN
8:10 am Chairperson’s Opening Remarks
Jonathan Essex, Ph.D., Head, Computational Systems Chemistry;
Chairman, Institute for Complex Systems Simulation (ICSS), School of
Chemistry, University of Southampton
8:15 Molecular Dynamics Drug Docking: Modeling Ligand
Interactions in the Age of High Performance Computing
Michael Kuiper, Ph.D., Computational Scientist, Victorian
Partnership for Advanced Computing
Continuing advances in computational performance now
allow researchers to routinely simulate protein molecules
in the order of hundreds of nanoseconds. At this timescale
it is possible to investigate detailed interactions of ligands
with receptors starting with the free ligand in solution. Though not
yet suitable for high-throughput drug screening, molecular dynamics
drug docking (MDDD) however does offer researchers an approach to
observe complex drug/ligand interactions not typically considered in
drug design.
8:40 The Internet is Here to Stay: Web Service Delivery of
Computational Properties
David Thompson, Ph.D., Senior Principal Systems Engineer,
Boehringer Ingelheim GmbH
A robust and extensible web services framework for the
delivery of computational properties to the medicinal
chemist’s desktop will be presented. This architecture fully
leverages our High Performance Compute environment,
exposes a wide variety of computational engines, and can be utilized
in a manner that best fits the scientists’ requirements. Use cases
including the consumption of in silico physicochemical properties and
the distribution of quantitative structure-activity relationship (QSAR)
models will be described.
FREE ENERGY APPROACH TO
STRUCTURE-BASED DRUG DESIGN
9:05 The Binding Energy Distribution Analysis Method
(BEDAM) for Structure-Based Drug Design: Theory and
Applications
Ronald M. Levy, Ph.D., Board of Governors, Professor of Chemistry &
Chemical Biology, Rutgers University
The binding energy distribution analysis method (BDEAM) for structurebased
drug design is a new approach to computing protein-ligand
binding free energies which makes use of replica exchange molecular
dynamics simulations to compute absolute binding affinities. The
balance between binding enthalpy and entropy is seen in our formalism
as a balance between unfavorable and favorable binding modes. Both
the theory and application of BEDAM will be discussed.
9:30 Fragment-Based Screening by Free Energy Simulations
Jonathan Essex, Ph.D., Head, Computational Systems
Chemistry; Chairman, Institute for Complex Systems
Simulation (ICSS), School of Chemistry, University of
Southampton
Free energy simulation is potentially a very powerful tool
for structure-based drug discovery. In this presentation,
the application of a number of these techniques to locate and score
molecular fragments and water in protein binding sites are described.
These approaches offer advantages over more conventional simulation
methods in that not only is fragment binding ranked in terms of
free energy (i.e. entropy is included), but all fragments are in direct
competition with water for the binding site.
9:55 A New Computational Method for Predicting Binding
Free Energies of Protein-Ligand Interactions
Christopher Langmead, Ph.D., Associate Professor of Computer Science,
Carnegie Mellon University
This presentation will discuss a new computational method, called
GOBLIN, for performing physics-based free energy calculations under
protein and ligand flexibility. GOBLIN compactly encodes Boltzmann
distributions over structures by exploiting conditional independencies.
Results on HIV-1 PR will be presented demonstrating that it achieves
superior quantitative accuracy than competing methods.
10:20 Small Covalent Peptidomimteic Inhibitors of Crm1
Mediated Nuclear Transport
Sharon Shechter, Head of Computational Discovery, Karyopharm
Therapeutics Inc
Nucleo-cytoplasmic transport of macromolecules is a fundamental
process of eukaryotic cells. Translocation of proteins and many RNAs
between the nucleus and the cytoplasm is carried out by shuttling
import and export receptors. CRM1 (Xpo1) is a major exporter
for proteins from the nucleus to the cytoplasm, including tumor
suppressors (TSPs) and other growth regulatory proteins (GRPs).
Here, we describe the identification of novel Crm1 inhibitors using
computational, hierarchical structure-based discovery process.
10:35 Networking Coffee Break in the Exhibit Hall with Poster
Viewing
»»
KEYNOTE PRESENTATION
11:00 Millisecond-Long Molecular Dynamics Simulations of
Proteins on a Special-Purpose Machine
David E. Shaw, Ph.D., Chief Scientist, D. E. Shaw Research
and Senior Research Fellow, Center for Computational
Biology and Bioinformatics, Columbia University
Molecular dynamics simulation provides a potentially
powerful tool for understanding the behavior of proteins
at an atomic level of detail, but its relevance to drug
design has previously been limited in part by the computational
demands of such simulations. We have constructed a specialized
supercomputer, called Anton, that has simulated the behavior
of a number of proteins for periods as long as a millisecond --
approximately 100 times the length of the longest such simulation
previously published -- revealing pharmaceutically relevant aspects
of protein dynamics that were previously inaccessible to both
computational and experimental study.
11:45 SZMAP: Mapping Solvent Sponsored by
Thermodynamics in Binding Sites
Anthony Nicholls, Ph.D., President & CEO,
OpenEye Scientific Software
Semi-continuum solvent theory captures discrete effects that can
be important in enclosed spaces such as binding cavities. Using this
model, SZMAP rapidly maps thermodynamic quantities of water
molecules near protein surfaces by employing a single explicit water
probe. The resulting quantities may be used as a correction factor for
continuum solvent calculations as well as serving to guide the design
of ligand analogues and optimizing binding affinity.
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12:05 pm Molecular Field Based Virtual
Sponsored by
Screening and Molecular Design
Jascha Blobel, Ph.D., Product Manager,
Sales & Product Development, Intelligent Pharma
By comparing molecular fields amongst molecules, it is possible
to find structurally different molecules with the same biological
functions. The molecule mimics are generally selected from a
compound database. Depending on the database type, different
information can be deduced, such as finding mechanisms of action,
hit identification, etc. However, the use of predefined databases sets
limitations in the identification of innovative molecules. In order to
overcome this problem, Intelligent Pharma has developed an artificial
intelligence system with a novel molecule designer which finds
innovative active molecules in the unexplored chemical space.
12:20 Luncheon Presentations (Sponsorship Opportunities
Available) or Lunch on Your Own
NEW TARGETS AND DRUG MODALITIES
1:30 Chairperson’s Remarks
Ruben Abagyan, Ph.D., Professor, Skaggs School of Pharmacy and
Pharmaceutical Sciences, University of California, San Diego
1:35 Structure-Based Ligand Discovery for GPCRs
Ruben Abagyan, Ph.D., Professor, Skaggs School of
Pharmacy and Pharmaceutical Sciences, University of
California, San Diego
The recent structures of GPCRs give us a better
understanding of the binding pockets for both antagonist
and agonists and insights into the structural mechanism
of the receptor activation. Computational approaches to structurebased
docking and modeling of pockets of subtypes and homologues
are presented along with successful application of these methods
to finding and optimizing GPCR modulators. Results of the recent
docking and modeling assessment (a.k.a. GPCR Dock 2010) for
CXCR4 with small molecule and a peptide, as well as the dopamine
receptor D3, are reviewed.
CO-LOCATED WITH:
Cambridge Healthtech Institute’s Ninth Annual
Next-Gen Kinase Inhibitors
Across Multiple Therapeutic Areas
June 6-8, 2011
healthtech.com/kin
Exhibit & Sponsorship Opportunities
Structure-Based Drug Design presents your company
with the opportunity to network with decision-makers and
leading professionals from throughout the biopharmaceutical
community. By participating as a Sponsor and Exhibitor,
your company can identify new business leads, market new
technology and increase brand awareness, while positioning
itself as a thought-leader amongst qualified buyers.
Opportunities include:
Sponsored Presentation
Present your scientific research and solutions for 15 or 30 minutes
as part of the conference program, ensuring your audience is seated
and ready to listen.
Breakfast & Luncheon Presentations
Invite session delegates to enjoy breakfast or lunch on your
company’s behalf while you give a 30-minute presentation. Your
workshop is concluded with 15 minutes of Q&A, allowing you to
interact with your customer base.
Exhibitor Information
The exhibit hall presents and excellent opportunity to network with
over 120 prominent scientists and executives who attend the event
to learn about cutting edge research and technologies in their field.
Exhibiting will allow your company to meet hard to reach prospects
face to face, and pave the way for future sales. Exhibit space fills up
quickly, so reserve yours today!
To find out more about our comprehensive sponsorship and exhibit
packages, please contact:
Katelin Fitzgerald
Manager, Business Development
781-972-5458
kfitzgerald@healthtech.com
HOTEL & TRAVEL INFORMATION
Conference Hotel:
Royal Sonesta Hotel Boston
40 Edwin Land Boulevard
Cambridge, MA 02142
Phone: 617-806-4200
Fax: 617-806-4232
Discounted Room Rate: $249 s/d
Discounted Room Rate Cut-off Date: May 10, 2011
Please visit our conference website to make your reservations online
or call the hotel directly to reserve your sleeping accommodations.
Identify yourself as a Cambridge Healthtech Institute conference
attendee to receive the reduced room rate. Reservations made
after the cut-off date or after the group room block has been filled
(whichever comes first) will be accepted on a space- and rateavailability
basis. Rooms are limited, so please book early.
Please visit healthtech.com/sbd for flight and hotel discounts.
Lead Sponsoring Publications:
The Intro-Net offers you the opportunity to set up
meetings with selected attendees before, during
and after this conference, allowing you to connect
to the key people you want to meet. This online
system was designed with your privacy in mind and
is available only to registered session attendees of
this event. Registered conference attendees will
receive more information on accessing the Intro-Net
in the weeks leading up to the event!
Sponsoring Publication:
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Web Partners:

2:00 The Role of Recent Crystal Structures of Membrane
Bound Proteins in Drug Discovery for CNS Targets
Sid Topiol, Ph.D., CSO, Computational and Structural
Investigations, 3D-2Drug
I would present illustrations of the impact of recent X-ray
structure determinations for the more challenging CNS
targets, i.e., membrane bound proteins. For class C GPCR’s,
new opportunities for drug discovery are being identified
using X-ray structures of the extracellular regions. Other targets, such
as transporters and ion channels, are also now amenable to structurebased
drug design.
2:25 Hitting a Moving Target: Characterizing GPCR Signaling
through Long-timescale Molecular Dynamics Simulations
Ron Dror, Ph.D., Senior Research Scientist and Special
Advisor to the Chairman, D. E. Shaw Research
A mounting body of evidence indicates that drugs
induce GPCRs to interconvert between numerous
conformational states with distinct intracellular signaling
profiles. Recent advances in algorithms and hardware for
molecular dynamics (MD) simulations are now bringing the previously
inaccessible timescales on which these transitions occur within reach.
This talk will describe ongoing studies of GPCRs using state-of-the-art
MD simulations, which have provided a hitherto elusive glimpse of the
conformational dynamics underlying GPCR-mediated signaling by both
endogenous ligands and drugs.
2:50 Networking Refreshment Break
3:00 Beyond the Orthosteric Binding Site: A Structure-Based
SAR Analysis of the D3R Selective Compounds
Lei Shi, Ph.D., Assistant Professor, Department of Physiology
and Biophysics, HRH Prince Alwaleed Bin Talal Bin Abdulaziz
Alsaud Institute for Computational Biomedicine, Weill Cornell
Medical College
Selective targeting of dopamine D3 receptor (D3R) has
therapeutic implications in neuropsychiatric disorders and
drug additions. D3R selective compounds have two pharmacophores
and a connecting linker. The talk will highlight individual and combined
contributions of these components towards the selectivity in the
context of the D3R structure. A novel structure-based design scheme
to address specificity issues of highly homologous GPCRs will be
presented.
3:25 Moving in New Circles – Exploiting Macrocycles for Drug
Discovery
Nick Terrett, Ph.D., CSO, Ensemble Therapeutics Corp
Macrocycles are largely underexploited in drug discovery
because they are generally perceived as structurally
complex and difficult to access. Ensemble Therapeutics has
developed platforms for the rapid synthesis and screening
of macrocycles in order to identify leads for challenging
protein-protein interaction targets. The talk will focus on the design and
synthesis of macrocycle libraries and the successful discovery of novel
lead molecules with unprecedented activity and drug-like properties.
DRUG RESISTANCE
3:50 Strategizing to Develop Resistance-Proof Inhibitors
Bruce Tidor, Ph.D., Professor of Biological Engineering and
Computational Science, Massachusetts Institute of
Technology
The selection of resistant variants is an important problem
limiting the therapeutic usefulness of inhibitors to targets
undergoing rapid mutation, particularly for applications in
infectious disease and cancer. We report our work exploring general
strategies for the development of inhibitors that have a reduced
tendency to induce resistance, using HIV protease as a trial target.
4:15 Computational Approaches to Modeling the Emergence
of Drug Resistance
Ryan Lilien, M.D., Ph.D., Assistant Professor, Department of
Computer Science & Donnelly Centre for Cellular and
Biomolecular Research, University of Toronto
The emergence of drug resistance reduces the
effectiveness of many novel therapeutics. I will describe
computational methods for predicting resistance mutations
through their structural and functional effects on the protein target.
These methods may allow us to identify new ways to create drugs that
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are less likely to be made ineffective by pathogen evolution, understand
the key determinants of the evolution and spread of resistance, and
develop the ability to slow the emergence of resistant variants.
4:40 End of Conference

Structure-Based
Cambridge Healthtech Institute and Bio-IT World Present the Eleventh Annual
Drug Design
Rational
June 8-10, 2011 • Royal Sonesta Hotel Boston • Cambridge, MA
Pricing Information
To Register, visit healthtech.com/SBD
P: 781.972.5400 or Toll-free in the U.S. 888.999.6288 | F: 781.972.5425 | E: reg@healthtech.com
Use Keycode 115100F when registering!
Structure-Based Drug Design Only (June 8-10)
Excludes dinner short course
Commercial
Early Registration Discount until March 11, 2011 $1395 $695
Advance Registration Discount until April 29, 2011 $1545 $775
Registration rate after April 29 and onsite $1745 $875
Structure-Based Drug Design & Next-Gen Kinase Inhibitors (June 6-10) Best Value
Includes dinner short course
Early Registration Discount until March 11, 2011 $2540 $1270
Advance Registration Discount until April 29, 2011 $2690 $1340
Registration rate after April 29 and onsite $2890 $1390
Dinner Short Course (June 8) $695 $395
conference discounts
Molecular
Approaches to Targeted
Therapeutics — From
Fragments to Biology
Academic, Government, Hospital-affiliated
Poster Submission - $50 OFF! Poster abstracts are due by May 4, 2011. Once your registration has been fully processed, we will send
an email containing a unique link allowing you to submit your poster abstract. If you do not receive your link within 5 business days, please
contact jring@healthtech.com. *CHI reserves the right to publish your poster title and abstract in various marketing materials and products.
International Society for Computational Biology (ISCB) Member Discount - 10% OFF! Subject to verification
REGISTER 3 - 4th IS FREE: Individuals must register for the same conference or conference combination and submit completed registration
form together for discount to apply.
GROUP DISCOUNTS AVAILABLE! Special rates are available for multiple attendees from the same organization.
For more information on group discounts, contact David Cunningham at +1-781-972-5472.
cAN’T MAKE IT TO Structure-Based Drug Design
Purchase the conference CD for $350 (plus shipping). Massachusetts delivery will include sales tax.
Each registration includes all conference sessions, posters and exhibits, food functions, and a copy of the conference proceedings link.
Handicapped Equal Access: In accordance with the ADA, Cambridge Healthtech Institute is pleased to arrange special accommodations for attendees with special needs. All requests for such assistance must be submitted
in writing to CHI at least 30 days prior to the start of the meeting.
To view our Substitutions/Cancellations Policy, go to http://www.healthtech.com/regdetails. Video and/or audio recording of any kind is prohibited onsite at all CHI events.
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list of reports, visit InsightPharmaReports.com, or contact Rose LaRaia,
rlaraia@healthtech.com, +1-781-972-5444.
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Please refer to the Registration Code below:
Cambridge Healthtech Institute
250 First Avenue, Suite 300, Needham, Massachusetts 02494
T: 781-972-5400 or toll-free in the U.S. 888-999-6288
F: 781-972-5425 • www.healthtech.com