Ligand-Induced Protein Conformational Changes

Identify and prioritize the most promising drug candidates earlier by measuring ligand-induced protein conformational changes under near-physiological conditions.

Drug discovery teams routinely screen large numbers of compounds and prioritize candidates based on affinity and kinetic parameters. Yet compounds with similar binding characteristics often behave very differently in downstream studies.

Traditional screening technologies provide valuable information about binding, but they typically do not answer critical questions such as whether a compound induces a desired conformational change. Structural biology techniques can provide mechanistic insights, but their throughput, sample requirements, and experimental constraints often limit their use in compound screening campaigns.

The result: larger candidate pools, higher development risk, costly late-stage failures, and slower project timelines.

Molecular Friction Sensing adds a new decision-making dimension to drug discovery workflows, enabling scientists to rank compounds not only by binding but also by their impact on protein structure. Screening-compatible and highly sample-efficient, the assay delivers actionable mechanistic insights that help reduce downstream risk and accelerate hit-to-lead and lead optimization programs. Based on the technology described in our featured preprint.

• Rank Compounds by Conformational Effect
  Move beyond simple binder identification. Compare and rank compounds based on their ability to induce biologically relevant conformational changes.
• Screening-Compatible Throughput
  Generate mechanistic insights without sacrificing screening efficiency. The assay is designed to support compound triaging and candidate ranking within drug discovery workflows.
• Measure Under Near-Physiological Conditions
  Perform experiments in biologically relevant buffer conditions without crystallization or extensive sample modification, preserving native-like protein behavior.
• Reduce Late-Stage Risk
  Support data-driven go/no-go decisions with an additional orthogonal readout. Identify the highest-quality candidates earlier and focus resources on molecules with the greatest probability of success.
• Low Sample Consumption
  Obtain conformational information using approximately 2 pmol of protein per measurement, helping conserve valuable samples.
  
  

For scientists seeking deeper mechanistic understanding, Molecular Friction Sensing bridges the gap between traditional binding assays and classical structural biology approaches.

Explore the scientific foundation of this novel approach and discover how conformational information can be used as an orthogonal screening parameter for compound prioritization.

In the preprint, researchers demonstrate how conformational readouts reveal differences between compounds that cannot be distinguished by affinity measurements alone.

Add mechanistic insight to your screening strategy and identify the candidates most likely to succeed.