Probing the Twisted Structure of Sickle Hemoglobin Fibers via Particle Simulations.

Polymerization of sickle hemoglobin (HbS) is the primary pathogenic event of sickle cell disease. For insight into the nature of the HbS polymer fiber formation, we develop a particle model-resembling a coarse-grained molecular model-constructed to match the intermolecular contacts between HbS molecules. We demonstrate that the particle model predicts the formation of HbS polymer fibers by attachment of monomers to rough fiber ends and the growth rate increases linearly with HbS concentration. We show that the characteristic 14-molecule fiber cross section is preserved during growth. We also correlate the asymmetry of the contact sites on the HbS molecular surface with the structure of the polymer fiber composed of seven helically twisted double strands. Finally, we show that the same asymmetry mediates the mechanical and structural properties of the HbS polymer fiber.