Structural stability of R-state conformation of carbonmonoxyl sickle and normal hemoglobin dimer

Abstract

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 $\approx$ (0.67 ± 0.06) kcal/mol.

Communicated by Ramaswamy H. Sarma

Keywords:

• Dimer
• R-state conformation
• hydrophobic interaction
• hydrogen bond
• free energy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contribution

JP carried out all the works, RPK supports for simulation run and NPA conceived the idea for the study. All authors read and approved the final manuscript. All data and paper are available with the correspondent author.

Data availability statement

All data that support the findings of this study are included within the article (and any supplementary files).

Table 2. vdW and electrostatic interaction energy (kcal/mol) in sickle Hb protein dimers.

Additional information

Funding

JP acknowledges University Grants Comission, Nepal for the Ph.D. Reasearch Grants of S & T-13/2076-77. We acknowledges the TWAS research grants RG 20-316.