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Beta-thalassemia is a genetic blood disorder represented by anomalies in hemoglobin’s beta chain production. Most hemoglobin defects are a result of mutations of the structural β-globin gene. Many diseases, including β-thalassemia, benefit from computational studies that aid researchers in investigating the association of genotype and phenotype. In this study, the alanine substitution mutations of the β-globin protein sub-units in the Turkish population (Hb Ankara, Hb Siirt and Hb Izmir) and the effects of those mutations on the β-globin protein structure and performance are examined using molecular dynamics simulation. While Hb Ankara variant showed a non-conservative mutation, Hb Siirt and Hb Izmir showed a semi-conservative mutation. RMSF values of Hb Siirt, between residues 95 and 99, were higher than wild-type and the other mutant proteins. The residues of Hb Ankara showed lower fluctuation compared to the other structures. The mean ROG values were 1.47 nm, 1.46 nm, 1.49 nm and 1.48 and the average number of the hydrogen bonds were 92, 100, 99, and 89 for Hb Ankara, Hb Siirt and Hb Izmir, respectively. Moreover, a significant increase in overall motion in Hb Siirt was observed based on PCA analysis. Hb Siirt substitution mutation might cause an effect in β-globin proteins which could impact the protein function. This indicates a major role on beta globin subunit’s stability for alanine on 27th position. However, Hb Ankara and Hb Izmir variants may act as a silent mutation, since these two mutations did not show a large change in the dynamics of the protein. Communicated by Ramaswamy H. Sarma