Malvern WAVEsystem (GCI) and PEAQ ITC for detecting weak interactions in drug discovery

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Fragment-based drug discovery (FBDD) is a powerful approach in modern drug development. It identifies promising drug candidates by screening small molecular fragments with low molecular weights that bind weakly but specifically to biological targets. However, detecting and characterising these weak interactions presents a significant challenge. Grating-coupled interferometry (GCI) and isothermal titration calorimetry (ITC) have emerged as essential tools for overcoming these hurdles, enabling researchers to validate fragment binding and gain deep kinetic and thermodynamic insights.

The Malvern WAVEsystem uses GCI, an advanced optical technique that provides real-time, label-free detection of molecular interactions. Unlike surface plasmon resonance (SPR), GCI uses waveguide-based interference, enhancing sensitivity for low-affinity fragments that may be missed using other methods. GCI detects weak-binding fragments, measures association and dissociation rates with precision, and enables efficient screening with minimal sample consumption. By identifying fragments with desirable kinetic profiles, GCI acts as a first filter in the FBDD workflow.

While the Malvern WAVEsystem (GCI) excels in kinetics, the Malvern PEAQ ITC provides a thermodynamic profile by measuring the heat released or absorbed during binding. It confirms hits detected by GCI and differentiates enthalpy- and entropy-driven interactions, offering insights into binding mechanisms. ITC also detects non-specific interactions and quantifies absolute binding constants, complementing GCI’s kinetic data.

Individually, the Malvern WAVEsystem (GCI) and Malvern PEAQ ITC are powerful tools, but their combined use offers deep insights into fragment binding. While GCI identifies and ranks hits based on binding kinetics, ITC validates and characterises their thermodynamic properties. This combined data can guide structure-based optimisation, leading to high-affinity, drug-like molecules while reducing time to clinical candidates.

The complementary nature of these techniques means that no valuable fragment is overlooked and all critical binding characteristics are fully explored, making them useful tools for modern drug development.

To learn more or book your personal demo, contact ATA Scientific or visit https://www.atascientific.com.au/products/creoptix-wave/.