Molecular dynamics simulations indicate that deoxyhemoglobin, oxyhemoglobin, carboxyhemoglobin, and glycated hemoglobin under compression and shear exhibit an anisotropic mechanical behavior

Abstract

We developed a new mechanical model for determining the compression and shear mechanical behavior of four different hemoglobin structures. Previous studies on hemoglobin structures have focused primarily on overall mechanical behavior; however, this study investigates the mechanical behavior of hemoglobin, a major constituent of red blood cells (RBCs), using steered molecular dynamics (SMD) simulations to obtain anisotropic mechanical behavior under compression and shear loading conditions. Four different configurations of hemoglobin molecules were considered: deoxyhemoglobin (deoxyHb), oxyhemoglobin (HbO2), carboxyhemoglobin (HbCO), and glycated hemoglobin (HbA1C). The SMD simulations were performed on the hemoglobin variants to estimate their unidirectional stiffness and shear stiffness. Although hemoglobin is structurally denoted as a globular protein due to its spherical shape and secondary structure, our simulation results show a significant variation in the mechanical strength in different directions (anisotropy) and also a strength variation among the four different hemoglobin configurations studied. The glycated hemoglobin molecule possesses an overall higher compressive mechanical stiffness and shear stiffness when compared to deoxyhemoglobin, oxyhemoglobin, and carboxyhemoglobin molecules. Further results from the models indicate that the hemoglobin structures studied possess a soft outer shell and a stiff core based on stiffness.

Tetrapyrroles at near-ambient pressure: porphyrins and phthalocyanines beyond the pressure gap

“…This approach represents at the same time a rationale for explaining the different behavior of a same chromophore in different protein environments [38], and a starting point for the development of bottom-up 2D active systems based on tetrapyrrolic tectons at surfaces. As an example, already the simple mechanical deformation plays a role in the case of hemoglobin (figure 6) [39]. Oxygen binding shifts the Fe atom from outside the plane of the porphyrin into the plane and the proximal histidine residue gets pushed with it.…”

“…Consequently, the structural transition at the Fe ion in one of the four subunits of the protein is transmitted directly to the other subunits. This mechanism is at the basis of the nonlinear, cooperative absorption of oxygen in hemoglobin [2,39]. More in general, similar mechanisms are exploited in many metalloenzymes, representing approximatively one third of the known enzymes, and promoting a variety of reactions well beyond just absorption and transport, including bond cleavage and formation, electron transfer, atom transfer, and radical chemistry [40].…”

Molecular insights into the irreversible mechanical behavior of sickle hemoglobin

“…1b and 1d respectively). The alignment was performed by defining an imaginary tetrahedron with the iron atoms of the HEME residues as the corners and aligning its sides and corners consistently (Yesudasan et al, 2017) with the Cartesian coordinate system as explained next. Figure 2a shows the molecular representation of the hemoglobin molecule with α-chains and β-chains.…”

“…The equilibrated HbS strand was then compressed from both sides (Fig. 10a), using the compression strategy of rigid walls (Yesudasan et al, 2017). The time elapsed molecular representation of this compression procedure is visualized ( Fig.…”

“…The de-oxygenated state of HbS and HbA was used for these studies. Using the compression algorithm that has been previously developed (Yesudasan, Wang, & Averett, 2017), the solvated and non-solvated molecules were compressed and the resulting force versus deflection graph was used to estimate the stiffness of the molecules.…”