A new technique developed by an international research team will accelerate the discovery of drugs targeting ion channels – critical proteins involved in a wide range of diseases, from psychiatric disorders to cancer. The method, detailed in the Journal of the American Chemical Society, allows scientists to study drug-protein interactions directly within living cells, bypassing complex and potentially disruptive isolation procedures.
The Challenge of Ion Channel Drug Discovery
Ion channels regulate the flow of ions across cell membranes, playing essential roles in nerve transmission, muscle contraction, and immune response. Dysfunction in these channels is linked to numerous diseases, making them prime targets for therapeutic intervention. However, traditional drug discovery methods require isolating these proteins, a process that can alter their natural behavior and hinder accurate study.
A Breakthrough in Real-Time Analysis
The new technique utilizes nuclear magnetic resonance (NMR) to observe drug-protein interactions in real time, within living cells. This approach is faster (experiments completed in under an hour), more cost-effective, and simpler, eliminating the need for extensive protein purification. Researchers can now study how drugs bind to ion channels in a biologically relevant environment, leading to more accurate and reliable results.
Validating Computational Models
The team tested their method on P2X7 receptors, ion channels implicated in depression, autism spectrum disorders, and certain cancers. They successfully identified key drug-protein interaction points, enabling optimization for greater efficacy and specificity.
Crucially, the researchers combined experimental data with three-dimensional computer models of drug-receptor binding, developed at the Institute of Chemical Research (IIQ-CSIC-US). This allowed them to validate which computational models accurately reflected real-world observations, bridging the gap between theory and experiment.
Implications for Future Drug Development
“The interaction between drug and protein is like a lock and key: the membrane protein is the lock, and the drug is the key. We not only have to find the right key but also figure out how to insert it so that it opens more effectively,” explains Jesús Angulo of the Institute of Chemical Research.
The ability to validate computational models on living cells represents a paradigm shift in drug development targeting membrane proteins. This technique promises to accelerate the creation of more effective and targeted therapies for a broad spectrum of diseases.
This new approach streamlines the drug discovery process, enabling faster identification of promising compounds and reducing the reliance on time-consuming and potentially misleading isolation methods. The combination of real-time analysis and computational validation positions this technique as a standard tool for structure-activity studies, ultimately accelerating the development of life-changing therapies
