2nd NovAliX Conference - Biophysics in Drug Discovery 2015
Developing the Synergy between Biophysics and Medicinal Chemistry to Deliver Better Drugs
Strasbourg, France June 9-12, 2015
Molecular Recognition in Protein-Ligand Complexes
Prof. Gerhard KLEBE
PHILIPPS-UNIVERSITY MARBURG, Marburg, Germany Read more
Prof. Gerhard KLEBE
Gerhard Klebe is full professor for pharmaceutical chemistry at the University of Marburg, Germany. His research is directed towards the understanding of protein-ligand interactions using chemical synthesis, microcalorimetry, molecular biology, crystallography, bioinformatics and software development. Software tools such as CoMSIA, AFMoC, DrugScore, Relibase/Cavbase or MOBILE have been developed in the group. He studied chemistry in Frankfurt/M, obtained his PhD in physical chemistry and spent postdoctoral stays in France and Switzerland. In BASF he was responsible for molecular modeling and crystallography. In 2005 he refused an offer from ETH Zürich, for a chair in Pharmaceutical Chemistry, published more than 280 scientific papers, serves on the editorial board of several journals, was member of the Board of Governors of the CCDC and is on the advisory board of the Leibniz-Institute FMP in Berlin. In 2011 he received an ERC Advanced Grant to support the research of his group. He organizes in two years frequency an International Workshop on New Approaches in Drug Discovery and Design. Further details: www.agklebe.de.
SESSION 1: Method Development & Emerging Technologies
No Crystal, No Problem: Hydrogen Deuterium Exchange Mass Spectrometry in Drug Discovery
Dr Nino CAMPOBASSO
GLAXOSMITHKLINE, Collegeville, United States Read more
Dr Nino CAMPOBASSO
Nino’s interests are in structural biology tools to progress drug discovery efforts. He has developed tools at GSK to use structural models from crystallography to further understand target proteins in solution. This allows program teams to better understand structure function relationships, better characterize HTS hits and help influence Structure Activity Relationships (SAR).
Education & professional Experience:
BS Chemistry, University of Chicago;
PhD Biochemistry, Purdue University;
Research Associate & Lecturer, Cornell University
Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay
Dr Pär NORDLUND
KAROLINSKA INSTITUTE & NANYANG TECHNOLOGICAL UNIVERSITY, Singapore, Singapore Read more
Dr Pär NORDLUND
Pär Nordlund is Professor at Karolinska Institute, Sweden, and also run a research group at Nanyang Technological University, Singapore. Originally a structural biologist he now works in the area of molecular and cellular cancer research. Early work focused on structural and mechanistic studies of ribonucleotide reductases and protein phosphatases, but later the group has taking a systems structural biology approach for proteins in cancer processes. At the Karolinska Institute he funded the Swedish node of the Structural Genomics Consortia that solved 140 human protein structures during the period 2005-2010. His groups have developed expertise in membrane proteins and did in 2007 solve the first structure of a human integral membrane protein. The group has a strong track record in developing protein science technologies, most recently the cellular thermal shift assay (CETSA) for measuring drug drug-target interactions in cells and tissues, which is likely to be a valuable tool for drug development and diagnostics applications.
He is a member of the Nobel Assembly and the Swedish Academy of Science, as well as a reviewing editor for Science Magazine. He is also the co-funder of the biotech companies Sprint Bioscience (fragment based drug discovery), Pelago Bioscience (CETSA) and Evitra Proteoma (Protein engineering).
Second-Harmonic Generation (SHG) Measures and Resolves Protein Conformations: High-Throughput Structural Drug Discovery
Dr Joshua SALAFSKY
BIODESY, South San Francisco, United States Read more
Dr Joshua SALAFSKY
Dr. Salafsky is the Chief Scientific Officer and Founder of Biodesy, Inc. and the inventor of the SHG technique for detecting biological molecules and their conformational changes. Biodesy is currently engaged in collaborations wtih academic and Pharma scientists around the world and is launching their first commercial system in 2015. Prior to founding Biodesy, Dr. Salafsky was a postdoctoral fellow in the Dept. of Chemistry at Columbia University and the Dept. of Physics at Utrecht University in the Netherlands, as well as a guest researcher at the Cavendish Laboratory at the University of Cambridge, UK. During this time, he invented ‘SHG labels’ and worked in the field of photovoltaics. Dr. Salafsky’s expertise and interests are in the areas of Biophysics and Physical Chemistry. He received his Ph.D. from Stanford University where he studied the reaction center protein, the marvelous engine at the heart of photosynthesis that converts light into chemical energy.
SESSION 2: Biophysics for Integral Membrane Proteins
Fluorine NMR Screening: Principles and Application to a Membrane Protein
Dr Claudio DALVIT
UNIVERSITY OF NEUCHÂTEL, Neuchâtel, Switzerland Read more
Dr Claudio DALVIT
Claudio Dalvit studied biophysics at the University of Trento, Italy, and trained at the Carnegie-Mellon University, USA, The Scripps Research Institute, USA, and the University of Lausanne, Switzerland. He joined Sandoz (now Novartis), Switzerland in 1989 as lab head prior to his position in 1999 as head of the biomolecular NMR group at Pharmacia & Upjohn, Italy and then senior scientist in the Drug Discovery & Development Department of the Italian Institute of Technology. He joined the University of Neuchâtel in 2011 as NMR expert in the NPAC unit of the Faculty of Science. His research interests are in NMR spectroscopy, from methodology development to its applications in chemistry and biology, fluorine chemistry, fragment-based drug discovery and enzymology. He is the recipient of the 2006 Gold Medal of the Italian society of magnetic resonance.
Improving the Biophysical Properties of GPCRs for Drug Screening and Structural Biology
Prof. Andreas PLÜCKTHUN
UNIVERSITY OF ZÜRICH, Zurich, Switzerland Read more
Prof. Andreas PLÜCKTHUN
Andreas Plückthun studied chemistry at the University of Heidelberg, and received his PhD at the University of California at San Diego. He was a postdoctoral fellow at the Chemistry Department of Harvard University. He became group leader at the Genzentrum and Max-Planck-Institut für Biochemie in Martinsried. He was appointed to the University of Zurich as a Full Professor of Biochemistry in 1993. He has written over 370 publications, which have been cited over 20,000 times (h-factor 84). In 2003, he was elected to the German Academy of Science (Leopoldina).
He received the Young Investigator's Award of the German Industry Fund, was elected member of EMBO, and is recipient of the Karl-Heinz-Beckurts-Prize (Munich, Germany), finalist in the World Technology Awards 2001 (London, UK), recipient of the JP Morgan Chase Health Award (San Jose, USA), the Wilhelm Exner Medal (Vienna, Austria), and together with his colleagues, the Swiss Technology Award (Bern, Switzerland) and the deVigier Award. He is co-founder and Scientific Advisor of Morphosys AG (Martinsried, Germany) and of Molecular Partners AG (Zürich, Switzerland), for which he is also a board member.
His research field is protein engineering. His lab combines directed evolution, biophysics and biomedical applications. His major contributions to the field include antibody engineering, the development of true Darwinian in vitro evolution technologies, the development of new binding proteins (DARPins) and the evolution of highly stable G-protein coupled receptors.
SESSION 3: Impact of Biophysics on Drug Discovery Projects
Biophysical Approaches for Hit Finding and Evaluation at Bayer
After studying physics and protein crystallography at the University of Heidelberg, Ursula received her Ph.D. in biology in 1987 at the University of Freiburg with Georg Schulz. For a Postdoc, she joined the protein crystallography group of Wolfram Saenger at the Free University of Berlin specializing in sequence analysis and homology modeling of protein-ligand complexes with a primary focus on herbicide binding proteins. In the early 1990s she moved to Schering AG, where she built up a homology modeling platform with an emphasis on obtaining appropriate force fields for low-molecular weight compounds. In addition she pursued the establishment of a bioinformatics platform linking structural biology information to bioinformatics data. Since 2000, she is Director of Structural Biology at Bayer Healthcare in Berlin. Ursula’s main research interest is to facilitate early small molecule drug discovery by druggability assessments of targets, X-ray crystallography and fragment screening for hit identification. Her group strongly contributes to lead generation and optimization mainly in the therapeutic areas of oncology and cardiology.
Making Every Interaction Count: Impact of Biophysical Methods Across the AstraZeneca Small-Molecule Portfolio
Current Title and Position:
Principal Scientist Biophysics, Discovery Sciences, Structure & Biophysics, AstraZeneca R&D Mölndal
Application of biophysical methods to facilitate the mechanistic understanding of protein-ligand interactions. This includes but is not limited to ligand binding kinetics and thermodynamics as well as mode of actions studies and proof of target engagement. Enabling fragment-based lead generation through a suite of biophysical screening methods including SPR and thermal shift assays as well as applying Cheminformatics for fragment expansion and fragment-assisted approaches.
Education & Experience:
I obtained my Ph.D. from the University of Frankfurt with focus on Biophysical Chemistry and NMR. Afterwards I helped to establish the Structural Chemistry Laboratory at Astra in Mölndal, Sweden. Before moving into my current role as Principal Scientist at AstraZeneca, I had different roles as Team leader protein engineering as well as Delivery leader for Neuroscience. I´ve been using biophysical methods for >20 years in support of research.
Some Examples of Biophysics Helping Drug Discovery
Prof. Rod HUBBARD
UNIVERSITY OF YORK & VERNALIS, Cambridge, United Kingdom Read more
Prof. Rod HUBBARD
Rod Hubbard has been working with methods for analysis and exploitation of protein structure for nearly 35 years. In the 1980s, he developed molecular graphics and modelling methods. In the 1990s he helped build the Structural Biology Lab at the University of York and determined the structure of many proteins of therapeutic importance; this was combined with studies of protein-ligand interactions and some of the first work in finding small fragments that bind to protein targets. Since 2001, he has spent varying amounts of his time with Vernalis, establishing and applying structure and fragment-based methods for drug discovery.
Biophysics and Structural Biology Enabling the Discovery of Therapeutic Solutions: from Small Molecule Inhibitors to Vaccine Design
Head of Translational Sciences Unit and Lead Generation France (Sanofi, France)
Vincent Mikol completed a Ph.D. in Biophysics at the University of Strasbourg, France, in 1989, where he studied protein crystallization. He then continued postdoctoral training at Sandoz (Basle, Switzerland) from 1990-91, working on the crystal structure determination of antibodies with the aim to develop biological therapeutics which culminated in the approval of Simulect®. He continued in Sandoz as a research scientist until he joined the Sanofi predecessor company Rhone-Poulenc Rorer in 1996 as head of structural biology. He continued his career with Sanofi focusing on drug design approaches which have led to several development candidates either small molecules or biologics in various therapeutic areas including immunology, oncology, anti-infectives, cardiovascular and neuro-degeneration. He is now running a multidisciplinary team combining genomics, biological, biochemical, biophysical and chemical approaches enabling drug discovery. He is the author of more than 50 original articles and patents.
SESSION 4: The Use of Kinetics in Drug Discovery
CCR2 Antagonists: From Structure-Kinetics Relatiosnhips to in vivo Efficacy
Dr Laura HEITMAN
UNIVERSITY OF LEIDEN, Leiden, The Netherlands Read more
Dr Laura HEITMAN
Laura H. Heitman, PhD. studied Biopharmaceutical Sciences at the University of Leiden, The Netherlands. In October 2004, she started as a PhD student on the project “Allosteric modulation of ‘reproductive’ GPCRs” at the Division of Medicinal Chemistry of Leiden University in collaboration with Organon/MSD in Oss, The Netherlands. In January 2009 she was appointed ‘tenure track’ assistant professor of molecular pharmacology in this division, and became 'tenured' associate professor as of November 2014. Her research interests are mainly focused on understanding and improving drug-receptor interactions, and more specifically, receptor residence time and allosteric modulation of GPCRs. In the last couple of years, she has obtained several competitive research grants, all allowing her to study these novel and highly translational concepts for drug action.
Towards a Better Understanding of the Structural Mechanisms of Kinase Inhibitor Binding Kinetics
Prof. Stefan KNAPP
OXFORD UNIVERSITY, Oxford, United Kingdom Read more
Prof. Stefan KNAPP
Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996) and continued his career at the Karolinska Institute as a postdoctoral scientist (1996-1999). In 1999, he joined the Pharmacia Corporation as a principal research scientist in structural biology and biophysics. He left the company in 2004 to set up a research group at the Structural Genomics Consortium at the University of Oxford (SGC). Since 2008 he is a Professor at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and since 2012 Director for Chemical Biology at the Target Discovery Institute (TDI). His research interests are the rational design of selective inhibitors that target protein kinases as well as protein interactions modules acting as reader domains of the epigenetic code.
Analysis of Binding Kinetics and Thermodynamics of DPP-4 Inhibitors and their Relationship to Structure
Herbert Nar is Director of the Structural Research Group at the Boehringer Ingelheim German Research Centre Biberach.
The group comprises units for protein expression and purification, biophysics of ligand binding, NMR and protein crystallography.
He graduated from the Technical University Munich in Chemistry and obtained his Ph.D. from the same institute.
After postdoctoral work with Robert Huber at the Max-Planck-Institute für Biochemie, Martinsried, Germany, he joined Boehringer Ingelheim to establish a protein crystallography laboratory, before taking over responsibility for the Structural Research Group.
He is author or co-author of >80 publications and >50 patents and was involved in numerous projects yielding clinical candidate chemical matter.
SESSION 5: Special Focus on Epigenetics
When to get Biophysical with Readers, Writers and Erasers
Dr Chun-wa CHUNG
GLAXOSMITHKLINE, Stevenage, United Kingdom Read more
Dr Chun-wa CHUNG
Current title and position: Group Leader of Structural and Biophysical Analysis, Computational and Structural Chemistry, GlaxoSmithKline R&D, Stevenage, UK
Research field: Application of structural biology (NMR, Xray) and biophysical methods (SPR, ITC, MS) for mode of action, hit triage and hit identification including fragment based screening. Particular interest in field of epigenetic drug discovery.
Education and past experience: BA Natural Sciences (Chemistry), University of Cambridge. PHD in NMR techniques development with Dr James Keeler, University of Cambridge.
Protein Methyltransferase Inhibitors as Personalised Cancer Therapeutics
Robert A. Copeland, Ph.D. is President of Research and Chief Scientific Officer at Epizyme, Inc. Dr. Copeland received his B.S. in chemistry from Seton Hall University, his doctorate in chemistry from Princeton University and did postdoctoral studies as the Chaim Weizmann Fellow at the California Institute of Technology. His research interest is in elucidating the determinants of drug recognition by their biological targets and the use of this information in the discovery and design of new medicines.. He has contributed to drug discovery and development efforts across a wide range of therapeutic areas leading to 17 drug candidates entering human clinical trials. These include the cancer drugs Tafinlar (Dabrafenib), Foretinib, Afuresertib and Mekinist (Trametinib) and the antibiotic Altabax (Retapamulin).
Interrogating the Bromodomain Family Through Chemical Biology
Dr Richard CUMMINGS
CONSTELLATION PHARMACEUTICALS, Cambridge, United States Read more
Rich Cummings is a senior research scientist working at the interface of biology and chemistry with a primary focus on enzymology, assay development, and lead discovery and validation.
Currently he is Senior Director of Lead Discovery at Constellation Pharmaceuticals. Prior to this he was at Merck Research Laboratories where he worked in a variety of areas including Cardiovascular Diseases, Infectious Diseases and High Throughput Screening.
His graduate training was in organic chemistry at Syracuse University. Subsequently he did postdoctoral studies in enzymology at Harvard Medical School.
Characterization of IL17A Inhibitors by Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS)
As a principal research scientist at Lilly-Spain, Alfonso has been working almost exclusively in the application of hydrogen deuterium exchange-mass spectrometry (HDX-MS) to study protein-ligand interactions for the last three years. In his role, he pushes the HDX-MS technology further and applying it to the drug discovery space including protein-protein interactions, epigenetics, ion channel receptors, etc. Focusing in LC-MS methodologies, Alfonso is co-author of several peer review papers and book chapters.
A Universal Homogeneous Assay for High-Throughput Determination of Binding Kinetics
Amaury Fernández-Montalván is a Research Scientist at the Berlin’s Lead Discovery Unit of Bayer Pharma AG. He studied Biochemistry in the University of Havana and obtained his PhD from the Technical University of Munich with a dissertation on the mechanisms of regulation and catalysis of calcium-dependent cysteine proteases. He then moved to Basel, Switzerland to become a postdoc in the Expertise Platform Proteases of the Novartis Institutes of Biomedical Research, where he investigated the biochemistry and enzymology of ubiquitin specific proteases. Two years later he was awarded with a WHO/TDR fellowship to pursue the discovery of drugs against tropical neglected diseases work in the Molecular Pharmacology and Screening Department of Merck Serono International S.A. (Geneva, Switzerland). In 2008 he joined Bayer, where his current responsibilities include developing and performing biochemical and biophysical screening assays to support hit identification, hit-to-lead, and lead optimization campaigns.
* Currently a postdoc at AstraZeneca R&D, leading the initiative to develop a single molecule microscopy platform for biophysical screening applications.
* Ph.D. in Biophysics from Chalmers University of Technology, Sweden
* M.Sc. in Biochemical engineering from Chalmers University of Technology, Sweden
* Author of >10 high impact publications (JACS, Nano Letters)
* Co-inventor on 2 patent applications
First Crystal Structure of Transmembrane Domain of G-Protein-Coupled Receptor MGLU5 Provides Insight Into Efficient New Drugs Design
Dr Krzysztof OKRASA
HEPTARES THERAPEUTICS, Welwyn Garden City, United Kingdom Read more
Dr Krzysztof OKRASA
Dr Krzysztof Okrasa has over 10 years experience working with enzymes/proteins expression, purification, crystallization and characterization by mass spectrometry. He has two Ph.Ds. which he received from Université Paris-Sud and Warsaw University of Technology. He worked as a researcher in academia at The University of Minnesota (USA), at The Centre of Excellence for Biocatalysis, Biotransformations and Biocatalytic Manufacture, University of Manchester (UK) and at The University of St. Andrews (UK). In 2011 he moved to industry and joined Heptares Therapeutics as a Senior Scientist to work on GPCRs. At Heptares Therapeutics he established and manages mass spectrometry facility to provide analytical support for GPCRs characterisation.
CDK8 Inhibitors with Long Residence Time Emerging from a Retro-Design Approach: New Opportunities for Cancer Treatment
Dr Anita WEGERT
MERCACHEM-SYNCOM, Nijmegen, The Netherlands Read more
Dr Anita WEGERT
* Since 05/2014- Senior Project Manager Medicinal Chemistry at Mercachem, Nijmegen
* 10/2008-04/2014 - Project lead and laboratory head in „Medicinal Chemistry“ at Grünenthal GmbH, Aachen
* 01/2007-09/2008 - PostDoc at Merck KGaA, Darmstadt (Synthesis of fluorinated building blocks and natural analogues)
* 02/2006-12/2006 - PostDoc at DSM-Nutritional Products AG, Kaiseraugst, Switzerland (synthesis development and optimization in the field of carotenoids)
* 07/2003-01/2006 - Doctoral thesis at the University of Rostock in the group of Prof. Dr. R. Miethchen, “Bioactive compounds based on fluorinated carbohydrates – Synthesis of N- and C-glycosides of selected furanoses and pyranoses”
* 11/2002-06/2003 - Diploma thesis at the University of Rostock in the group of Prof. Dr. R. Miethchen “Addition of CBrClF2 to L-Rhamnal and following reactions.”
Marta Westwood, obtained Ph.D. in 2013 in nanomaterials from Cranfield University.
I joined UCB in 2011 as a senior scientist within the Structural Biology group led by Alaistair Lawson. For the past three years I have been developing expertise in small molecule drug discovery using a fragment based approach. I have also been involved in the assay development for a novel antibody-enable drug discovery approach. Prior to joining UCB I was awarded a Postdoctoral Fellowship at the Institute of Food Research in Norwich to study the mono and multilayer films used to encapsulate active ingredients for a controlled and site-specific delivery within the GIT. During my time at IFR I worked on numerous projects including a commercial project for Pfizer focused on AFM imaging of proteins and polysaccharides. I have also been part of the team under the leadership of Claudio Nicolletii investigating the outcome of consumption of the probiotic L. casei Shirota in subjects with Seasonal Allergic Rhinitis.