A Coarse-Grained Molecular Dynamics Model for Sickle Hemoglobin Fibers

The intracellular polymerization of deoxy sickle cell hemoglobin (HbS) has been identified as the main cause of sickle cell disease. Therefore, the material properties and biomechanical behavior of polymerized HbS fibers have been a topic of intense research interest. A solvent-free coarse-grained molecular dynamics (CGMD) model has been developed and it represents a single hemoglobin fiber with four tightly bonded chains, each of which comprises soft particles. A harmonic spring potential, a bending potential, a torsional potential, and a Lennard-Jones potential are introduced along with a Langevin thermostat to simulate the behavior of a polymerized HbS fiber in the cytoplasm. The parameters of the potentials are identified via comparison of the simulation results with the experimentally measured values of bending and torsional rigidity of single HbS fibers. The proposed model is able to very efficiently simulate HbS fibers of 20 nm diameter and on the order of μm length-scale and μs time-scale. The model is validated by comparison with published experimental results and then it is used to investigate the interaction between two HbS fibers, and to study the fiber zippering process during heterogeneous fiber growth.