DAY TWO I MARCH 27, 2025

8:15 am Check In & Morning Refreshments

8:50 am Chair’s Opening Remarks

Discovering Biophysical Frontiers: The Emerging Techniques & Technologies to Enhance Drug Discovery

9:00 am Computationally Guided Design & Testing of De Novo Miniproteins

Synopsis

  • Using generative AI we design 45-60 amino acid miniproteins to bind to desired targets
  • We developed a high throughput production platform to express, purify and characterize thousands of unique miniprotein sequences
  • Data we generate is used to further optimize the computational tools and improve affinity and developability of hits

9:30 am Tailored Biophysical Methods For Soluble Enzymes & Transmembrane Receptor Targets

  • Arne Rufer Expert Scientist & Science & Technology Lead, Lead Discovery, Roche

Synopsis

  • Introduction to the enzymes and transmembrane receptor targets being studies by Roche
  • Complementary structural, direct binding and enzyme kinetics data for elucidation of small molecule mode of action
  • Chemical probe approaches facilitating characterization of GPCR-ligand interactions 

10:00 am Using Single Molecule Tracking For In-Cell Interactions & a Closer Look At Particle Dynamics for Detailed Understanding of Biological Processes

  • Laura Caccianini Postdoctoral Researcher, Massachusetts Institute of Technology

Synopsis

  • Implementing direct visualization of molecular interactions in real-time for the quantification of binding kinetics and affinities and identification of conformational changes induced by drug binding for improved efficacy
  • Exploring the many uses of probing protein dynamics, e,g, to measure diffusion coefficients and anomalous diffusion, characterization of protein-protein interactions for better understanding and discovery
  • Understanding drug transport and cellular uptake by tracking the movement of drug molecules within cells, visualization of drug delivery mechanisms and cellular uptake pathways and assessment of drug distribution and localization in tissues

10:30 am Morning Break & Networking

Analysing Case Studies in Biophysical Approaches to Target Selection, Hit Identification, Mechanism Exploration and Hit-To-Lead Studies To Improve Knowledge & Aid Future Drug Discovery

11:00 am Combined Screening and Optimization Approaches Enable Discovery of Highly Selective Kinase Inhibitors

Synopsis

  • Targeting kinases with specific small molecule inhibitors holds promise for treating diseases with high unmet medical need, but discovering such selective kinase inhibitors remains a major challenge
  • Combined insights from biophysical, biochemical, cellular, and modeling studies, as well as structure-based design enabled the discovery of highly selective compounds with a suitable set of properties for a proof-of-concept study
  • Unexpectedly, high selectivity was achievable despite the significant conservation of active site residues, suggesting a key role of dynamics and solvent effects in driving inhibitor selectivity

11:30 am Unlocking RNA as a Small Molecule Target Through Biophysical & Structural Techniques

Synopsis

  • Understand the advantages of targeting RNA in diseases with difficult protein targets
  • Discuss a novel and differentiated platform that utilizes biophysical techniques to evaluate small molecule compounds against RNA targets
  • Highlight how an integrative structural biology platform accelerates RNA-targeted drug design

12:00 pm Lunch

1:00 pm Hit Validation at the Extremes of Protein Size

Synopsis

Take-aways:

  • Case study on discovering validated chemical matter for a DNA-binding domain
  • Using a combination of experimental and computational techniques to validate fragment starting points and to drive SAR
  • Optimized RED-MS method and it’s application to hit-validation of hits to large protein complexes

1:30 pm Biophysical Insights for Deubiquitinases Chemical Matter

  • Ben Levin Principal Scientist, Stablix Inc.

Synopsis

  • Introduction to Stablix and Targeted Protein Stabilization (TPS) and hit ID chemical matter
  • Characterization of DUB chemical matter
  • Expanding horizons for biophysical characterization

2:00 pm Panel Discussion: Considering the Future Directions of Biophysics in Drug Discovery

Synopsis

  • Highlighting cutting-edge, biophysical techniques that are revolutionizing our understanding of biological systems to accelerate drug discovery
  • Exploring the future requirements in techniques for advancing current approaches
  • Investigating the current challenges and methods for solving them for improved discovery

3:00 pm Chair’s Closing Remarks

3:15 pm End of Conference Day 2

Conference Day One
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