Investigation of the human mutant aquaporin-2 (AQP2) proteins with molecular dynamics simulation

Aquaporin-2 is a channel protein located in the apical membrane of cells in the renal collecting duct, activated by vasopressin to regulate water reabsorption and urine concentration. Mutations on the Aquaporin-2 protein may affect the reabsorption of water in the kidneys disrupting the structure and function of the protein; leading to a rare kidney disease characterized by excessive urination known as Nephrogenic Diabetes Insipidus. This study aims to model and perform molecular dynamics simulations of the A45T, R85X, and A147T mutations identified and functionally analyzed in the Aquaporin-2 gene of patients diagnosed with Nephrogenic Diabetes Insipidus and to compare the results with experimental and other simulation results. Through the use of molecular dynamics simulations, the passage of water through the cell membrane has been demonstrated at the molecular level, and the channel structure of wild-type Aquaporin-2 and its mutants has been investigated. As a result, it has been observed that the modeled mutant proteins within the scope of the thesis allow the passage of water molecules at different rates compared to wild-type Aquaporin-2, and thus show varying degrees of functional changes. It is believed that all the results obtained from the thesis study will contribute to understanding the diseases related to water balance and the development of relevant treatment-drug methods.