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International Journal for Multiscale Computational Engineering
IF: 1.016 5-Year IF: 1.194 SJR: 0.452 SNIP: 0.68 CiteScore™: 1.18

ISSN Print: 1543-1649
ISSN Online: 1940-4352

International Journal for Multiscale Computational Engineering

DOI: 10.1615/IntJMultCompEng.v8.i2.80
pages 237-244

Molecular Modeling of Normal and Sickle Hemoglobins

Tao Wu
New Jersey Institute of Technology, Newark, New Jersey 07102, USA
X. Sheldon Wang
Midwestern State University
Barry Cohen
New Jersey Institute of Technology, Newark, New Jersey 07102, USA
Hongya Ge
New Jersey Institute of Technology, Newark, New Jersey 07102, USA


Sickle cell anemia is the first disease whose genetic cause was pinpointed at the DNA level. Sickle cell disease is caused by the switch of a single DNA base pair in the hemoglobin gene from A to T, which in turn changes an amino acid in the hemoglobin protein from glutamic acid to valine. Normal hemoglobin at this location is slightly hydrophilic and tends to form a protective layer of surrounding water molecules. Hemoglobin molecules, which are located in red blood cells and play a role in oxygen transport, assume a globular, or bead-like, shape. Their protective water coating tends to keep them separate from other hemoglobin molecules. In the mutated hemoglobin molecule, one normally hydrophilic spot becomes slightly hydrophobic and, in a deoxygenated state, tends to lose its protective layer of water molecules. The hemoglobin molecules consequently stick together and form a chain of hemoglobin beads. Moreover, such chains form bundles, eventually causing the red blood cell membrane, which is normally flexible and fluid, to become stiff and sticky. In the end, sickle cells tend to block capillary vessels and cause sickle cell anemia. In this paper, we present a molecular dynamics simulation of the mutated hemoglobin molecule interacting with another mutated hemoglobin molecule in aqueous environment. Singular value decomposition based principal component analysis is used for both spatial and temporal coarse grain models. Ultimately, we will use this red blood cell system (sickle or normal) to build a multi-scale and multi-physics modeling procedure ranging from molecular dynamics modeling of protein-protein interactions to immersed boundary/continuum methods for moving adhesive particles and soft fluid-solid continua.


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