In plain language: Dent’s disease is a rare genetic disorder caused by faults in ClC-5, a membrane protein that exchanges chloride ions for protons. Using simulations, Nostrum and IRB Barcelona scientists mapped step by step how ClC-5 works, then showed why a single-amino-acid deletion linked to the disease breaks it, even though the deletion barely changes the protein’s shape.
Why it matters to clients: Simulation can explain how a patient mutation causes disease when static structures cannot, a starting point for targeted and personalized therapies.
Published in PNAS Nexus, the study deciphers the sequence of structural changes that lets ClC-5 move chloride ions and protons in opposite directions, and how the 523ΔVal deletion disrupts this mechanism. It illustrates how state-of-the-art simulation methods can shed light on rare diseases and help identify targets for personalized medicine.
Read the full article in PNAS Nexus: https://doi.org/10.1093/pnasnexus/pgaf353
