'Computational protein design: from inception to an AI powered future'
Steve Mayo is the William K. Bowes Jr. Leadership Chair of the Division of Biology and Biological Engineering and Bren Professor of Biology and Chemistry at the California Institute of Technology in Pasadena, California. He has been a member of the Caltech faculty since 1992 and served as Vice Provost for Research from 2007 to 2010 before becoming Chair of the Division of Biology and Biological Engineering.
Mayo's research focuses on the development of computational approaches to protein engineering – a field that has broad applications ranging from advanced biofuels to human therapeutics. He co-founded Molecular Simulations Inc (Accelrys, now BIOVIA), a computational chemistry company; Xencor, a publicly traded bio-therapeutics company focused on developing next generation biologics for treating cancer; and, Protabit, a privately held protein engineering company.
Mayo was elected a member of the National Academy of Sciences in 2004 for his pioneering contributions in the field of protein design and was appointed by President Obama in 2013 to the National Science Board. He received his undergraduate degree in chemistry from the Pennsylvania State University, his Ph.D. in chemistry from Caltech, and did postdoctoral work at both UC Berkeley (chemistry) and Stanford (biochemistry).
'MicroED: conception, practice and future opportunities'
Dr Gonen is a Member of the Royal Society of New Zealand, a Professor of Biological Chemistry and Physiology at the David Geffen School of Medicine of the University of California, Los Angeles and an Investigator of the Howard Hughes Medical Institute. He is an expert in electron crystallography and cryo EM, determining the 1.9Å resolution structure of the water channel aquaporin-0 by electron crystallography, the highest resolution for any protein determined by cryo EM techniques at the time. Since 2011, Dr Gonen has worked as a Group Leader at the HHMI Janelia Research Campus where he has continued to work in electron crystallography, pioneering MicroED, a structural biology method with the potential to solve unknown structures at resolutions close to 1Å.
'Recent developments in data deposition, validation, biocuration, and archiving of MX, NMR, and 3DEM structure data in the Protein Data Bank'
Stephen Burley, M.D., D.Phil. is an expert in structural biology, proteomics, bioinformatics, structure/fragment based drug discovery, and clinical medicine/oncology. He currently serves as University Professor and Henry Rutgers Chair, Founding Director of the Institute for Quantitative Biomedicine, and Director of the RCSB Protein Data Bank at Rutgers, The State University of New Jersey. He is also a Member of the Rutgers Cancer Institute of New Jersey, where he Co-Leads the Cancer Pharmacology Research Program. From 2008 to 2012, Burley was a Distinguished Lilly Research Scholar in Lilly Research Laboratories. Prior to joining Lilly, Burley served as the Chief Scientific Officer and Senior Vice President of SGX Pharmaceuticals, Inc. Until 2002, Burley was the Richard M. and Isabel P. Furlaud Professor at The Rockefeller University and an Investigator in the Howard Hughes Medical Institute. He has authored/coauthored more than 260 scholarly scientific articles.
Monday Morning: Session 1 - Small Molecule Discovery 1
From Abl to EM, a journey in SBDD
Sandra Jacob, Novartis Institute for Biomedical Research
Conformational characterization of non-CDN STING agonists
Charles Lesberg, Merck Research Laboratories
Structure based design of novel inhibitors of the Mcl-1's protein-protein interaction
Xin Huang, Amgen Inc.
Session 2- NMR Biophysics Structure
If all models are wrong, how do we find the useful ones?
Martin Scanlon, Monash University
NMR spectroscopy ligand-dependent structural plasticity of TrkA kinase studied by NMR Spectroscopy
Reto Horst, Pfizer
Mechanistic characterization and crystal structures of small-molecule inhibitors of E.coli LpxA acyltransferase
Xiaolei Ma, Novartis Institute for Biomedical Research
Monday Afternoon: Session 3 - Biologics and Protein Design
Structure-based design and optimization of vaccine candidates
Enrico Malito, GlaxoSmithKline Vaccines
Understanding the mechanism of tetravalent biepitopic targeting by determining the
2.1 A ternary complex structure of OX40 bound to two agonistic fab fragments
Gladys de Leon Boenig, Genentech
Structural characterization of broadly neutralizing influenza antibodies isolated from human and non-human primates
Yu Qiu, Sanofi
Session 4 - Emerging Structure Technologies
Water molecules in protein-ligand interfaces
Paul Gibbons, Genentech
ProtaBank: a new database resource for the protein engineering community
Barry Olafson, Protabit, LLC
High-resolution structure determination to support drug discovery
Christopher Arthur, Genentech
Tuesday Morning: Session 5 - Cryo-EM in Drug Discovery
Cryo-EM at Astrazeneca: from molecular mechanisms of drug targets to SBDD
Taiana Maia de Oliveira, Astrazeneca
Cryo-EM resolves the multi-state activation mechanism of TPC channels
Alex Kintzer, Vertex Pharmaceuticals, Inc.
Cryo electron microscopy structures of voltage-gated sodium channels
Alexis Rohou, Genentech
An allosteric mechanism for potent inhibition of human ATP-citrate lyase
Byron de la Barre, The Consulting Biochemist
Tuesday Afternoon: Session 6 - Small Molecule Drug Discovery 2
SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate
Tom Clayton, Celgene
Structure analysis of Dipeptidyl peptidases DPP8 and DPP9 reveal inhibitor- and substrate-binding mode and cooperativity
Stephan Krapp, Proteros
Delineating the mechanism of the anti-cancer natural product nimbolide
Dirksen Bussiere, Novartis Institutes for Biomedical Research
Session 7 - X-ray Technology
Crystallography at the Advanced Light Source: current status and future opportunities
Corie Ralston, Advanced Light Source
Remote controlled protein to structure pipelines for drug design
Jose Antonio Marquez, European Molecular Biology Laboratory (EMBL)
Integrated structural biology platform at Diamond Light Source
Elizabeth Shotton, Diamond Light Source
De novo protein structure phasing for challenging targets
Hui Wang, Takeda
New opportunities at SSRL and LCLS for data collection and diffraction quality optimization under humidity controlled conditions
Aina Cohen, SSRL-SMB, SLAC National Accelerator Laboratory
Structural insights into inhibition of class I HDACs with novel zinc binding and nonbinding inhibitors
Daniel Klein, Merck
Structure determination of a novel dextran binding module in complex with isomaltohexaose
Yong Wang, Eli Lilly and Company
Biophysical characterization and structural studies of Small Multidrug Resistance family of transporters
Ali Kermani, University of Michigan
Development of a virtual reality platform for effective communication of structural data in drug discovery
Steve McCloskey, Nanome
Second-harmonic generation (SHG) – A novel on-target and high-throughput technology for small molecule screening by detecting structural changes of target biomolecules
Margaret Butko, Biodesy, Inc.
Protein domain trapping: high throughput protein engineering to enable biophysics and structural biology based drug discovery
Denys Pogoryelov, Zobio BV
Structures of RANKL with denosumab molecular structure
Athena Sudom, Amgen
NanoImaging Services, Inc. – a one-stop solution for outsourcing CryoEM
Annete Schneemann, NanoImaging Services, Inc.
Canadian Macromolecular Crystallography Facility (CMCF) upgrades: enabling higher flux and micro-focusing for versatile high-throughput MX studies
Michel Fodje, Canadian Light Source Inc.
Emerging technologies and X-ray crystallography (it's hard to get a crystal structure without a crystal)
Andrew Bond, DeNovX
Fast molecular interaction screening of epigenetic gene regulator HMT G9a with fragments from a large chemical space using the Dianthus NT.23PicoDuo
Lindsay Dawson, NanoTemper Technologies
Wuxi Biortus: a cryo-EM CRO company for drug discovery in China
Lei Jin, Wuxi Biortus Biosciences Co., Ltd.
Protein preparation for structure biology in industrial settings is in transition as new techniques are introduced. Our panel will discuss differences in protein requirements for X-ray crystallography versus Cryo-EM, stabilization techniques for membrane proteins maintaining the functional state, data bases as tool to efficient construct design, and offer attendees to ask detailed questions regarding upscale and purification approaches, most useful analytical equipment and new developments in supporting software.
Sujata Sharma (Janssen Research & Development) - Moderator
Kathleen Aertgeerts (Vertex Pharmaceuticals)
Aaron Thompson (Janssen Pharmaceuticals)
Byron DeLaBarre (The Consulting Biochemist)
Anatrace / Molecular Dimensions
There are a wide range of new technologies and techniques now available to explore the connections between protein structure and function. The recent availability of bright X-ray microbeams and advanced automation at synchrotrons, the use of high-speed pixel array detectors for diffraction and Cryo-EM measurements, and the advent of X-ray Free Electron Lasers (XFELs), has enabled the examination of biological systems that were previously inaccessible. Such procedures such as room temperature serial crystallography on nano-crystals, in-situ crystallization and diffraction screening, controlled dehydration and on-site integration of X-ray results with Cryo-EM are now becoming readily available to the industrial community. The panel will discuss how these advances will benefit the structural biologist in a drug discovery setting and will answer attendees' questions on where they see these multiple developments taking the industrial user in the future.