Beyond affinity: Screening Protein Conformational Responses by Molecular Friction Sensing

The compound that binds best isn't always the one that works. Compounds with similar affinity and kinetics often behave very differently downstream - because binding alone doesn't reveal how a molecule reshapes its target. In this webinar we are unveiling Molecular Friction Sensing on heliX⁺, a newly published approach for detecting ligand-induced conformational changes in proteins with sub-Ångström sensitivity under near-physiological conditions. Binding-induced modulation of protein structure is central to how many small-molecule drugs work, yet most screening platforms rely on affinity-based readouts that don't report conformational change. By resolving structural effects independently of affinity or kinetics, Molecular Friction Sensing adds an orthogonal decision-making dimension to hit-to-lead and lead optimization, helping you prioritize the most promising candidates earlier. Presenting the science behind the recently released preprint, this session shows how the assay works, what it reveals, and how it fits alongside your existing biophysical toolkit. In this webinar, Prof. Ulrich Rant (Technical University Dresden, Kurt-Schwabe-Institute for Sensor Technologies, Bruker Dynamic Biosensors) will explain how to: • Rank compounds by their impact on protein conformation, not just by binding affinity • Detect subtle, small-molecule-dependent structural changes using surface-tethered DNA-origami nanolevers and nanolever-velocity readout • Generate mechanistic insight at screening-compatible throughput, using ~2 pmol of protein per measurement • Reduce late-stage risk with an additional, orthogonal readout for confident go/no-go decisions