CONFERENCE DAY TWO - Thursday, June 13
7:00 am Check-In & Light Breakfast
7:55 am Chair’s Opening Remarks
From Small Molecules to Peptides to Biologics: Dealing with Hard-to-Drug, Dynamic, Proteins with the Structural Biology Toolbox – Case Study Presentations
8:00 am Unleashing the Potential: Cryo-Em’s Impact to Effectively Supercharge Structural Determination
Synopsis
- Using Cryo-EM to answer different questions in drug discovery projects, exploring why and when to use cryo-EM
8:30 am Resolving Sample Bottlenecks through Advanced CryoEM Grid Hardware
Synopsis
- Exploring cryo-em sample preparation
- Highlighting cryo-em grids
8:45 am Application of Cryo-EM for Structure-Based Design Against Membrane Protein Targets
Synopsis
- Rationalising drug design by harnessing the state-of-the-art techniques in structurebased drug design
- Utilizing structures to increase understanding of the system
9:15 am Integrated Structure-Guided Drug Discovery accelerates success in early discovery research: A worked example from a challenging DNA-repair target, Artemis
Synopsis
- Designing a new protein construct that provided the first crystal structure of Artemis
- Discussing a unique screening library produced novel hits to an allosteric binding site
- Highlighting efficient SAR development was enabled by more than 80 co-crystal structures and collaborative efforts of medicinal and computational chemistry
- Understanding without these structures key induced-fit effects could not have been predicted
9:45 am Structure-Based Vaccine & Antibody Discovery at AstraZeneca
Synopsis
- Leveraging Cryo-EM in structure-based design of novel vaccine candidates
- Highlighting structural determination of MoA for neutralising antibodies against respiratory viruses
10:15 am Morning Break
10:45 am Harnessing a Hybrid Approach Including X-Ray Crystallography, NMR, Cryo-EM, HDX, & Machine Learning to Accelerate the Discovery & Development of Vaccines
Synopsis
- Combining and supporting structure-based vaccine identification, characterization and design with a combination of methods across discovery and development
- Utilising machine learning to accelerate the identification of new vaccine using 3D protein structure information
11:15 am Driving Vaccine Design & Antibody Discovery Using Cryo-EM
Synopsis
- Illuminating the cryo-EM pipeline to evaluate polyclonal antibody responses
- Increasing throughput of cryo-EM sample evaluation
- Sequencing antibodies directly from cryoEM data and highlighting epitope mapping
11:45 am Capitalizing on Structure Biology to Target the Oncogenic State of RAS Mutants with RAS(ON) Tri-Complex Inhibitors
Synopsis
- Exploring the rational design of a natural product-inspired small molecule created a neomorphic surface on an intracellular chaperone cyclophilin A that was exploited to target active KRASG12C with high affinity and selectivity
- Harnessing further structure-guided optimization to design a novel, non-covalent compound with broad activity across the active state of multiple oncogenic (H/K/N) RAS variants
- Showcasing the preclinical data to demonstrate the Tri-complex inhibitors selectively target active KRASG12C or multiple RAS mutants and are now in clinical trials
12:15 pm Lunch & Networking
1:45 pm Illuminating a Structural Engineering-Based Approach for Interrogating NUAK1 Kinase Selective Inhibitors
Synopsis
- Designing a dynamic human NUAK1-MARK3 crystallographic chimera
- Exploring a robust crystallizable construct, navigating SAR
1:45 pm Structure Empowered IMAPCT Platform in the Discovery & Development of Immunoglobulin Sculpting (IgSc) Enzyme & Dual-Cell Bidirectional (DcB) Antibody Drugs for Immunological Diseases
Synopsis
- Understanding the structural biology function and IMPACT platform
- Exploring how structure-based rational design and machine learning design fueled drug discovery and development of IgSc enzyme
- DcB antibody-antigen structures supporting the development of biologic drugs
Overcoming Structural Complexity in Drug Delivery & Formulation Development
2:15 pm Molecular Understanding of Drug Delivery and Stability From Solution and Solid-State NMR Spectroscopy
Synopsis
- Utilizing real-world examples to highlight structural challenges encountered in drug development
- Employing molecular insights from NMR to enhance drug design, focusing on improving delivery and stability
- Appreciating interdisciplinary learning and collaboration between structural biophysics and pharmaceutical sciences
Emerging Technologies in Structure-Based Drug Design: Shaping the Future of Protein Structure Determination
3:15 pm Advancing the Development & Applications of Time-Resolved Cryo-EM
Synopsis
- Understanding the importance and specific challenges posed by conformational dynamics to rational drug discovery
- Exploring the development of time-resolved sample preparation for cryo-EM and single particle analysis to address these challenges
- Discussing relevant areas of application
3:45 pm Afternoon Break
3:45 pm Enabling In-Cell Structural Biology by Large-Scale Site-Specific Photo- Crosslinking
Synopsis
- In-cell photocrosslinking to map direct protein-protein contacts at single residue resolution
- Photocrosslinking to unravel the architecture of GR-Hsp90-cochaperone complexes
- Applications to functional studies and pharmacology
4:15 pm Panel Discussion: Looking to the Future of Structure-Based Drug Design: Driving Resolution & Speed
Synopsis
- Exploring recent advancements in Cryo-EM, AI prediction, and more to push the resolution boundaries
- Maximising integrating approaches for enhanced resolution and functional insights
- Exploring the potential of cloud computing and collaborative platforms to make SBDD accessible and facilitate drug development
- Delving into the practicalities of incorporating AI and machine learning
- Assessing structure-based drug design as a continuous feedback loop to inform structure-based optimization