Investigation of Aquaporin-2 and its mutants with molecular dynamics simulations

OpenAlex İngilizce

Aquaporin-2 (AQP2) is a crucial water channel protein localised to the apical membrane of renal collecting duct cells, which regulates water reabsorption in response to vasopressin. Nephrogenic Diabetes Insipidus (NDI) is a rare disorder characterised by excessive urine production, often resulting from mutations in the AQP2 gene. In this study, we performed molecular dynamics simulations on three AQP2 mutations (A45T, R85X, A147T) previously identified in Turkish patients diagnosed with NDI and functionally characterised in Xenopus oocytes. This study systematically analyses the structural and functional impacts of these specific mutations. Our computational results reveal significant alterations in water permeability and channel integrity in mutant AQP2 proteins, which correlate well with prior experimental mutation analysis. This study, uniquely linking computational predictions to experimental findings, deepens the molecular understanding of NDI pathogenesis and highlights potential therapeutic targets. To the best of our knowledge, this is the first study demonstrating a direct correlation between in silico and in vivo assessments of AQP2 mutations.