Aquaporins are water transporting channels, present in mammals, plants, bacteria, yeast, and amphibians facilitating the osmoregulation of water as well as some small solutes. Aquaporin Z (AqpZ), a water-selective aquaporin from E. coli strain, specifically transporting water by rejecting all other types of solutes and ions, has become a popular choice in biomimetic channels used for water filtration due to its efficiency and specificity. This study is focused on exploring effects of point mutations in/near the conserved Selectivity Filter (SF) of AqpZ, which are F208W, F208T, F208C, F208K, F43Y, F43S, F43A, F43D, R189T, H174T, T183S and T183S/F208W. Using all-atom MD simulations, we analyzed their impacts on conformational changes, structural stability, pore radius and the water permeability rate. The free energy profiles were calculated using PMF calculation and MM-GBSA methods to evaluate the structural integrity of the tetrameric assembly. While most single point mutations did not significantly alter the conformations of conserved residues but notable changes were observed in loop flexibility and arginine189 gate, disrupting the hydrophobicity of pore and the channel permeability. Among mutants, F208W increased the water permeability by 10 percent, while F43D resulted in a blocked channel leading to a loss of functionality and a double mutant T183S/F208W has the wildtype-like behavior and functional characteristics. The findings indicate that the improved channel’s permeability does not necessarily correlate with pore size but with the delicate balance of polar and hydrophobic interactions in the SF region. The study underscores the critical role of conserved residues in regulating the channel’s functionality.