Welcome Address
Session 1: Recent Advances in FBDD
Session Chair
Dr Mike HANN
GSK MEDICINES RESEARCH CENTRE, Stevenage, United Kingdom
After completing his PhD on the synthesis of Enkephalin derivatives in 1980, Mike worked as a medicinal chemist at Wyeth and GD Searle, also developing an interest in computational chemistry at the latter. Mike joined Glaxo in 1986 and was responsible for helping build and then lead the computational chemistry, biophysics, x-ray and chemical biology departments. He helped develop fragments theory and practice for lead identification1. His current role is in developing new technologies for early drug discovery approaches, including attrition reduction2, chemical biology for target tractability assessment4, and understanding drug distribution at cellular and subcellular resolution3. Mike is a GSK Senior Fellow and an Adjunct Professor in the chemistry department at Imperial College London.
1. Hann, Michael M.; Leach, Andrew R.; Harper, Gavin. Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery. Journal of Chemical Information and Computer Sciences (2001), 41(3), 856-864.
2. Hann, Michael M. Molecular obesity, potency and other addictions in drug discovery MedChemComm (2011), 2(5), 349-355.
3. Kristin K. Brown, Michael M. Hann, Ami S. Lakdawala, Rita Santos, Pamela J. Thomas and Kieran Todd. Approaches to target tractability assessment – a practical perspective. Med. Chem. Commun., 2018,9, 606-613.
4. André Mateus, Laurie J. Gordon, Gareth J. Wayne, Helena Almqvist, Hanna Axelsson, Brinton Seashore-Ludlow, Andrea Treyer, Pär Matsson, Thomas Lundbäck, Andy West, Michael M. Hann, and Per Artursson. Prediction of intracellular exposure bridges the gap between target- and cell-based drug discovery PNAS July 25, 2017 114 (30) E6231-E6239.
PhABits – Shining New Light on Fragments Approaches for Assessing Targets Tractability (IL01)
Fast Molecular Interaction Screening and Affinity Determination in Biophysical Drug Discovery Projects with Dianthus NT.23 and Tycho NT.6 (OC01)
Mr Andreas LANGER
NANOTEMPER TECHNOLOGIES GMBH, Munich, Germany
Targeting TIR Domain Assemblies in TLR Signaling Pathways to Design Anti-Inflammatory Compounds (OC02)
Mr Md Habibur RAHAMAN
UNIVERSITY OF QUEENSLAND, Brisbane, Australia
Ligand-Based Fluorine NMR Screening in Drug Discovery (IL02)
Dr Anna VULPETTI
NOVARTIS, Basel, Switzerland
Anna Vulpetti received her Ph.D. degree in Chemistry from the University of Milan (Italy) in 1994 working on the development of a new synthetic route for paclitaxel side chain synthesis. In 1995 she joined the Computer Aided Drug Design group of Pharmacia & Upjohn, and in 2006 she moved to Novartis, where, as Senior Investigator, she supports drug discovery projects in multiple disease areas and develops computational methods. Anna's research interests include the development of novel methods for describing and comparing binding sites, fragment-based drug discovery, and the better understanding of the role of fluorine in drug design. In 2005 she was awarded with the Farmindustria Prize for Young Scientists Excelling in Pharmaceutical Chemistry.
Coffee Break & Exhibition
Exhibitor Short Presentation: Crelux – A WuXi AppTec company
A Fragment-Based Approach to Leverage Challenging Targets: Human STING
19F NMR Screening Applied to Multiple Cancer Target (OC03)
Dr Kenneth CAMERON
CRUK BEATSON INSTITUTE, Glasgow, United Kingdom
Enabling Drug Discovery with Crude Reaction Mixture Screening (IL03)
Dr Ben DAVIS
VERNALIS RESEARCH, Cambridge, United Kingdom
Dr Ben Davis is a Research Fellow at Vernalis Research, a biotech company based in Cambridge UK which has been at the forefront of fragment-based approaches since 1998. An NMR spectroscopist and biophysicist by training, his research focus is developing and applying biophysics and FBLD methods to enable drug discovery for challenging therapeutic targets and systems.
Dr Davis studied for his PhD in protein folding and ligand binding with Professor Alan Fersht at Cambridge University, and then worked on a wide range of molecular interactions in both academia and biotech companies. He has over 20 years' experience in the drug discovery industry, has contributed to six books over the last decade and is an author on more than thirty scientific publications. He is a frequent speaker at scientific conferences and has been running FBLD training workshops since 2007.
Academia Keynote Lecture
Structure-biophysics Driven PROTAC Design for Degrading Undruggable Cancer Targets (KL01)
Prof. Alessio CIULLI
UNIVERSITY OF DUNDEE, Dundee, United Kingdom
Alessio Ciulli holds the Personal Chair of Chemical and Structural Biology at the School of Life Sciences, University of Dundee. His research interests are in chemical biology, structural biology and drug discovery of protein-protein interactions (PPIs) within the chromatin and ubiquitin-proteasome systems. Of particular interest are the development and application of small molecules approaches for inducing protein degradation, and chemical genetics and fragment based drug design approaches to target protein surfaces and PPIs.
Alessio graduated in Chemistry (2002) from his hometown Florence under the late Ivano Bertini and obtained his PhD from the University of Cambridge (Chemistry, 2006), studying as a Gates Cambridge Scholar under the supervision of Chris Abell and in collaboration with Astex Pharmaceuticals. Following post-doctoral research on fragment-based drug design with Chris Abell and Tom Blundell, and an HFSP visiting Fellowship at Yale University to begin collaboration with Craig Crews (2009), he was awarded a BBSRC David Phillips Fellowship and returned to Cambridge to start his independent career in 2010. In 2013 Alessio was awarded an ERC Starting Grant and moved his laboratory to the School of Life Sciences at Dundee to take up a Readership and Principal Investigator role within the Division of Biological Chemistry and Drug Discovery. He was promoted to Professor in October 2016. He is a Fellow of the Royal Society of Chemistry. Alessio is the recipient of several prizes and awards, including:
- 2014 Talented Young Italian award
- 2015 EFMC Prize for Young Medicinal Chemist in Academia
- 2015 ICBS Young Chemical Biologist Award
- 2016 RSC Capps Green Zomaya Award in medicinal computational chemistry
- 2016 MedChemComm Emerging Investigator Lectureship.
Session 2: Challenging Targets (GPCRs, Ion Channels...)
Structural Biology of Seven-Transmembrane Receptors Toward Drug Discovery (IL04)
Prof. Shigeyuki YOKOYAMA
RIKEN, Yokohama City, Japan
Dr. Shigeyuki Yokoyama currently leads the RIKEN Yokoyama Laboratory. He is also a Visiting Professor at Juntendo University School of Medicine, an Emeritus Professor of the University of Tokyo, and Foreign Honorary Member, American Academy of Arts & Sciences. He has received numerous awards including the 56th Fujihara Award, Academic Award of Mochida Memorial Foundation for Medical and Pharmaceutical Research, and Takeda Medical Science Prize.
His research has been focused on the structural biology of proteins and nucleic acids, with a special emphasis on gene expression (transcription and translation) and on proteins participating in cell signaling systems involving extracellular ligands, transmembrane receptors etc., by using X-ray crystallography and NMR spectroscopy. The purpose of his research is to understand the molecular mechanisms underlying the functions of complex cellular machines consisting of many molecules, by analyzing the protein conformations and molecular functions. Among his many favorite targets, he has spent much time studying RNA polymerase, tRNAs, and aminoacyl-tRNA synthetases. He expanded his study to structural biology of integral membrane proteins and some of his recent results covered the structural determinations of Adiponectin receptors, Claudin family proteins and leukotriene B4 receptor BLT1.
On the basis of his research on genetic systems (particularly the translation system), novel technologies, such as cell-free protein production technologies and the expanded genetic code systems utilizing unnatural base pairs and amino acids, have been developed. The cell-free protein synthesis method produces proteins by the in vitro use of the cellular translation machinery. His group dramatically improved the method to enable the production of challenging protein samples, such as huge, unstable complexes and human integral membrane proteins. For the genetic-code systems engineering, his team developed aminoacyl-tRNA synthetase mutants by molecular engineering on the basis of their crystal structures, and integrated them into Escherichia coli and mammalian cells to incorporate non-natural amino acids site-specifically into proteins. These technologies have successfully been used to understand protein functions, including human epidermal growth factor receptor (EGFR) signaling; voltage-gated sodium channel β subunits, with which, β subunit-mediated cell-cell adhesion mechanisms were revealed with structure-based mutagenesis and site-directed photo-crosslinking analyses.
Venturing into the Untapped: Discovery of Small-Molecule Drugs Targeting Messenger RNAs Using Biophysical and Computational Methods (OC04)
Dr Ella MORISHITA
VERITAS IN SILICO, Tokyo, Japan
Cryo-EM Structures Capturing the Transport Cycle of the P4-ATPase Flippase (OC05)
Mr Masahiro HIRAIZUMI
MITSUBISHI TANABE PHARMA CORPORATION, Yokohama, Japan
Masahiro received an M.S. degree in Biological Sciences from the University of Tokyo in 2016. He explored the structure of ion channels using X-ray crystallography under the guidance of Dr. Osamu Nureki. After graduating from college, he joined Mitsubishi Tanabe Pharma Corporation and worked as a researcher on the Structural Biophysical Team. He is currently sent from his company to the University of Tokyo to study cryo-EM as a PhD student.
Advancing Cryo-EM for Determination of G Protein-Coupled Receptor Structure (IL05)
Prof. Patrick M. SEXTON
MONASH UNIVERSITY, Parkville, Australia
Professor Sexton is a NHMRC Senior Principal Research Fellow at the Monash Institute of Pharmaceutical Sciences, Monash University. He is a leader in the study of GPCRs, biased agonism, on allosteric interactions between GPCRs and other proteins, and small molecule ligands. Prof. Sexton has received numerous awards including the ASCEPT Lecturer award, Endocrine Society of Australia Senior Plenary award, ASCEPT Rand Medal, Vane Medal (British Pharmacological Society (BPS)), and the GSK award for Research Excellence. He is also a Clarivate Analytics Highly Cited Research (Pharmacology & Toxicology). Prof. Sexton is an adjunct Professor of Fudan University in Shanghai, a member of the SAB for the Chinese National Centre for Drug Screening, an elected Fellow of the BPS and Editor-in-Chief for ACS Pharmacology and Translational Science.
Lunch Break, Exhibition & Networking
Session 3: Cryo-EM in Drug Discovery
Cryo-EM Structural Studies of The Human TRPV4 Ion-Channel: Insights and Characterization of a Novel Open-Conformation (OC06)
Dr Simon HOLTON
BAYER, Berlin, Germany
Cryo-EM Application for Drug Discovery (OC07)
Dr Wen-ti LIU
Wen-ti Liu joined the cryo-EM lab of Holger Stark in Max Planck Institute for Biophysical Chemistry in 2009 and received her MSc and PhD there. After her study, she stayed as a junior postdoc focusing on optimizing biochemistry as well as cryo-EM for macromolecular complexes. She joined NovAliX in 2016 as the project manager for cryo-EM and participated in the establishment of the cryo-EM platform on site. Since then, she has been utilizing electron microscopy as a tool for analyzing structures of proteins with high pharmaceutical industry interest.
Advancing Drug Discovery in Pharma Using Cryo-EM (IL06)
Dr Claudio CIFERRI
GENENTECH, South San Francisco, United States
Claudio Ciferri began his career as an X-ray crystallographer. In 2006, he became a Postdoctoral Fellow working with Professor Eva Nogales at UC Berkeley. In 2011, he joined Novartis as a group leader, and in 2014, moved to Genentech with a goal to establish a world-class, industrial cryo-EM group. Since 2016 he is leading the cryo-EM effort at Genentech to support Research, Large and Small Molecule Drug Discovery.
Exhibitor Short Presentation: Thermo Fisher Scientific
Cryo-EM Single Particle Analysis Productivity: the State of the Art
Session 4: X-ray Crystallography / Cryo-EM Complementarity
Increased Performance in High-Throughput Compound and Fragment Screening Campaigns by the Use of "Club Class" Data Collection (IL07)
Dr Gerard BRICOGNE
GLOBAL PHASING LTD., Cambridge, United Kingdom
Gerard Bricogne is the founder and director of Global Phasing Ltd., a small non-profit research group specialised in methods and software for macromolecular X-ray crystallography (MX), supported mostly by a Consortium of pharmaceutical companies who make extensive use of its software. He started his PhD work in 1972 at the MRC-LMB in Cambridge under the supervision of David Blow (at a time when there were only 12 structures in the PDB) and has dedicated his whole research career to the field of mathematical and computational methods. He applied his PhD work on non-crystallographic symmetry to the solution of the first two virus crystal structures, then became interested in the role of probability theory in the direct solution of the phase problem. This led him to introduce Bayesian statistical methods into the areas of experimental phasing and structure refinement, implemented respectively in the SHARP and BUSTER programs from his group. His other interests have been in the improvement of processing methods for diffraction data, through an EEC Workshop held in 1986-89 whose influence is still felt today, and more recently in improving the design and conduct of diffraction experiments themselves, including their incorporation into large-scale compound screening campaigns by MX. His contributions to the advancement of crystallographic methods were recognised by the award of the Aminoff Prize of the Royal Swedish Academy of Sciences in 2009.
Discovery of a Regulatory Subunit of the Yeast Fatty Acid Synthase (IL08)
Prof. Holger STARK
MAX PLANCK INSTITUTE FOR BIOPHYSICAL CHEMISTRY, Göttingen, Germany
Holger Stark is a Professor at the University of Göttingen and a Director at the Max-Planck-Institute for biophysical Chemistry in Goettingen. He studied Biochemistry in Berlin and obtained training in electron microscopy and image processing at the Fritz-Haber-Institute in Berlin. After a postdoc at the Imperial College in London, he moved to Marburg to become a group leader and two years later he moved to Goettingen where he is since. In 2007 he was appointed as a full Professor and 2015 as a Director of the Max-Planck-Institute. The research of Holger Stark is focused on structure determination of large macromolecular complexes such as the ribosome, spliceosome, proteasome and several enzymatic complexes by cryo-EM and X-ray crystallography. The lab develops methods for improved biochemical sample preparation, image-processing software and is involved in the development of new electron microscopical hardware.
Applying Hybrid Biophysical and Structural Methods to Study Allosteric Regulation of GTP Cyclohydrolase I - A Target for Treating Inflammatory and Neuropathic Pain (IL09)
Dr Herbert NAR
BOEHRINGER INGELHEIM, Biberach, Germany
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 and focused on supporting small molecule and biologics drug discovery projects.
Herbert graduated in Chemistry at the Technical University Munich and obtained his Ph.D. from the same institute. After postdoctoral work with Robert Huber at the Max-Planck-Institut 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.
Posters & Drinks
Session 5: Hot Topics
Re-energizing Small Molecule Drug Discovery by Centaur Chemist™ (IL10)
Industry Keynote Lecture
From Fragments to Pharmaceuticals (KL02)
Dr Harren JHOTI
ASTEX PHARMACEUTICALS, Cambridge, United Kingdom
Harren Jhoti co-founded Astex in 1999 and was Chief Scientific Officer until November 2007 when he was appointed Chief Executive Officer. He was elected a Fellow of the Royal Society in 2018, the Royal Society of Chemistry in 2016, and of the Academy of Medical Sciences in 2015. In January 2018 he was honoured with a Lifetime Achievement Award from the UK BioIndustry Association (BIA). He received the Prous Institute-Overton and Meyer Award for New Technologies in Drug Discovery from the European Federation for Medicinal Chemistry in 2012 and was also named by the Royal Society of Chemistry as "Chemistry World Entrepreneur of the Year" for 2007.
Dr. Jhoti has published widely including in leading journals such as Nature and Science, and has also been featured in TIME magazine after being named by the World Economic Forum a Technology Pioneer in 2005. He has served on the board of the BIA, the UK BioIndustry Association and currently consults for life science venture capital firms. Before founding Astex in 1999, he was head of Structural Biology and Bioinformatics at GlaxoWellcome in the United Kingdom (1991-1999). Prior to Glaxo, Dr. Jhoti was a post-doctoral scientist at Oxford University. He received a B.Sc. (Hons) in Biochemistry in 1985 and a Ph.D. in Protein Crystallography from the University of London in 1989.
Session 5: Hot Topics (continued)
Exhibitor Short Presentation: NanoTemper Technologies
Biophysical Tools for Measuring Binding Affinity, Protein Stability or Protein Quality with just a Tiny Amount of Sample
Exhibitor Short Presentation: NovAliX
Single Particle Cryo-EM a Cutting Edge Service for Drug Discovery
Uncovering a Ligand-Induced Twisted State of a Homodimeric Enzyme by Pulsed Electron-Electron Double Resonance (OC08)
Dr Dzung NGUYEN
PHILIPPS-UNIVERSITÄT MARBURG, Marburg, Germany
Structural Mechanisms of and Drug Discovery Targeting Substrate of Gamma-Secretase in Alzheimer's Disease (OC09)
Prof. Chunyu WANG
RENSSELAER POLYTECHNIC INSTITUTE, Latham, United States
Chunyu Wang, associate professor of Biological Sciences at RPI, is an expert in NMR (nuclear magnetic resonance) structural biology and in structural mechanisms of Alzheimer's disease and cancer. He obtained his MD in 1996 from Peking Union Medical College (PUMC). He was then trained in structural biology at Cornell University under the guidance of Linda Nicholson, earning a PhD in Molecular Biology and Genetics in 2000. He carried out postdoctoral work at Columbia University in Art Palmer's group. After establishing his own research group at RPI in 2005, he developed a strong research program in structural mechanisms in protein autoprocessing and Alzheimer's disease. He has been awarded multiple grants from NIH and several grants for Alzheimer's research, from Alzheimer's Association, New York State and American Health Assistance Foundation (Now BrightFocus foundation). Recently, he started working on drug discover in AD with funding from the Warren Alpert Foundation. For more information, check out his lab website: http://homepages.rpi.edu/~wangc5/
Poster Prize and Closing Remarks
End of the Conference