Modeling sickle hemoglobin fibers as one chain of coarse-grained particles

Sickle cell disease is a genetic disorder most commonly found in people of African descent and it is caused by the presence of abnormal hemoglobin S (HbS) in the patient’s red blood cells (RBCs). In the deoxygenated state, the defective hemoglobin tetramers polymerize forming stiff fibers which distort the cell and change its biomechanical properties. Because the HbS fibers play a vital role in the formation of the sickle-shaped RBC, the material properties and biomechanical behaviors of polymerized HbS fibers is a subject of intense research interest. Here, we introduce a solvent-free coarse-grain molecular dynamics (CGMD) model to simulate a single hemoglobin fiber as a chain of coarse-grained particles. A finitely extensible nonlinear elastic (FENE) potential is applied between consecutive particles. Meanwhile, a FENE-type bending potential is employed to model the bending resistance of HbS fibers. The parameters of the potentials are identified via comparison between the simulation results and the experimentally measured values of bending rigidity of single HbS fibers. The Langevin thermostat is employed to control the system temperature. This model will greatly facilitate future studies on the HbS polymerization, fiber bundle and gel formation as well as the interaction of between the HbS fiber bundles and the RBC membrane. In addition, the model can be easily adapted to study other filamentous protein assembles.