A mutation at the sixth residue, glutamic acid to valine, in beta chain of hemoglobin distorts the entire shape of hemoglobin into a sickle shape. The investigation of the binding mechanisms of different chains of hemoglobin under the mutated condition can give an understanding of the molecular distortion. In this work, we have studied the binding mechanism between two chains in the dimer structure of the R-state conformation of carbonmonoxyl sickle hemoglobin and is compared with that of normal hemoglobin by using molecular dynamics simulations. The binding strength between α-chain (PROA) and β-chain (PROB) in hemoglobin dimer has been analyzed by estimating hydrogen bonds, salt bridges, hydrophobic interactions and non-bonded interactions (electrostatics and van der Waals). The quantitative estimation of aforementioned interactions depicts that the structural stability of normal hemoglobin dimer is found to be greater than that of sickle one. The outcomes of such interactions are also supported by the estimated free energy between the chains in R-state conformation of the dimers. The difference of binding free energy, calculated by utilizing the umbrella sampling technique, is found to be (0.67 ± 0.06) kcal/mol.Communicated by Ramaswamy H. Sarma.
Keywords: Dimer; R-state conformation; free energy; hydrogen bond; hydrophobic interaction.