Investigating the behavior of normal and sickle hemoglobin on a molecular level

Sickle cell disease, a genetic mutation in DNA, alters the hemoglobin protein in the body. It results in abnormally shaped red blood cells that cannot transport oxygen properly and have a short lifetime. Treatments for the condition require an understanding of how sickle cells compare to normal cells.

Powrel and Adhikari used molecular dynamics simulations to investigate the molecular configuration and elastic behavior of mutated and non-mutated hemoglobin. Their goal was to explore the fundamentals of sickle cell disease on a molecular level, which could have implications for practical treatment applications.

Hemoglobin contains four globin chains, two alphas and two betas. The authors simulated normal cells and cells with a single mutated beta chain in water. They evaluated the dynamics of the system with such important aspects as the hydrogen bond binding force in the beta chain, the solvent accessible surface area, and the van der Waals, electrostatics, hydrophobic, and salt bridge interactions.

The team found a larger force is required to separate the beta chain of normal hemoglobin in comparison to sickle hemoglobin. The non-mutated protein is stiffer than its mutated counterpart, and the various interactions differ as well.

“We understand how the different binding takes place in these sickle and normal hemoglobin chains,” said author Narayan Prasad Adhikari. “Since there is still a strong binding of the sickle cell with the other three chains, one cannot isolate it easily. In future medicine for this disease, we need to take that into account.”

The researchers plan to simulate sickle cell mutations in the other beta chain and study the binding free energy.

Source: “Elastic property of sickle and normal hemoglobin protein: Molecular dynamics,” by Jhulan Powrel and Narayan Prasad Adhikari, AIP Advances (2022). The article can be accessed at https://doi.org/10.1063/5.0086539 .