Abonnement à la biblothèque: Guest
Portail numérique Bibliothèque numérique eBooks Revues Références et comptes rendus Collections
International Journal for Multiscale Computational Engineering
Facteur d'impact: 1.016 Facteur d'impact sur 5 ans: 1.194 SJR: 0.554 SNIP: 0.68 CiteScore™: 1.18

ISSN Imprimer: 1543-1649
ISSN En ligne: 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

RÉSUMÉ

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.

RÉFÉRENCES

  1. Bockzo, E., Cooper, T., Gedeon, T., Mischaikow, K., Murdock, D., Pratap, S., and Wells, K., Structure theorems and the dynamics of nitrogen catabolite repression in yeast. DOI: 10.1073/pnas.0501339102

  2. Brooks, B. R., Bruccoleri, R. E., Olafson, B. D., States, D. J., Swaminathan, S., and Karplus, M., CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. DOI: 10.1002/jcc.540040211

  3. Fogelson, A. L., A mathematical model and numerical method for studying platelet adhesion and aggregation during blood clotting. DOI: 10.1016/0021-9991(84)90086-X

  4. Fogelson, A. L., Wang, X., and Liu, W. K., Immersed Boundary Method and Its Extensions.

  5. Fung, Y. C., Biomechanics, Mechanical Properties of Living Tissues.

  6. Lim, S., Ferent, A., Wang, X., and Peskin, C. S., Dynamics of a closed rod with twist and bend in fluid. DOI: 10.1137/070699780

  7. Liu, Y., Zhang, L., Wang, X., and Liu, W. K., Coupling of Navier-Stokes equations with protein molecular dynamics and its application to hemodynamics. DOI: 10.1002/fld.798

  8. Lyman, E., Pfaendtner, J., and Voth, G. A., Systematic multiscale parameterization of heterogeneous elastic network models of proteins. DOI: 10.1529/biophysj.108.139733

  9. Schlick, T., Molecular Modeling and Simulation.

  10. Wang, X., Fundamentals of Fluid-Solid Interactions: Analytical and Computational Approaches.

  11. Zhu, C., Bao, G., and Wang, N., Cell mechanics: Mechanical response. DOI: 10.1146/annurev.bioeng.2.1.189


Articles with similar content:

MOLECULAR DYNAMICS PREDICTION OF ELASTICAND PLASTIC DEFORMATION OF SEMICRYSTALLINE POLYETHYLENE
International Journal for Multiscale Computational Engineering, Vol.9, 2011, issue 1
Severine Queyroy, Bernard Monasse
DIRECT NUMERICAL SIMULATION OF THE INTRA-VENTRICULAR FLOW USING PATIENT-SPECIFIC ANATOMY
TSFP DIGITAL LIBRARY ONLINE, Vol.7, 2011, issue
Trung Le, Iman Borazjani, Fotis Sotiropoulos
Emergence of a Mushy Region in Processes of Binary Melt Solidification
International Journal of Fluid Mechanics Research, Vol.26, 1999, issue 2
Dmitri V. Alexandrov, A. G. Churbanov, P. N. Vabishchevich
CONCURRENT ATOMISTIC-CONTINUUM MODEL FOR DEVELOPING SELF-CONSISTENT ELASTIC CONSTITUTIVE MODELING OF CRYSTALLINE SOLIDS WITH CRACKS
International Journal for Multiscale Computational Engineering, Vol.15, 2017, issue 2
Somnath Ghosh, Subhendu Chakraborty, Jiaxi Zhang
Therapeutic Targeting of BCR-ABL: Prognostic Markers of Response and Resistance Mechanism in Chronic Myeloid Leukaemia
Critical Reviews™ in Oncogenesis, Vol.17, 2012, issue 1
Timothy P. Hughes, David T. Yeung