A Coarse-Grained Molecular Model for Glycosaminoglycans: Application to Chondroitin, Chondroitin Sulfate, and Hyaluronic Acid
Author(s)Bathe, Mark; Rutledge, Gregory C.; Grodzinsky, Alan J.; Tidor, Bruce
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A coarse-grained molecular model is presented for the study of the equilibrium conformation and titration behavior of chondroitin (CH), chondroitin sulfate (CS), and hyaluronic acid (HA)—glycosaminoglycans (GAGs) that play a central role in determining the structure and biomechanical properties of the extracellular matrix of articular cartilage. Systematic coarse-graining from an all-atom description of the disaccharide building blocks retains the polyelectrolytes’ specific chemical properties while enabling the simulation of high molecular weight chains that are inaccessible to all-atom representations. Results are presented for the characteristic ratio, the ionic strength-dependent persistence length, the pH-dependent expansion factor for the end-to-end distance, and the titration behavior of the GAGs. Although 4-sulfation of the N-acetyl-D-galactosamine residue is found to increase significantly the intrinsic stiffness of CH with respect to 6-sulfation, only small differences in the titration behavior of the two sulfated forms of CH are found. Persistence length expressions are presented for each type of GAG using a macroscopic (wormlike chain-based) and a microscopic (bond vector correlation-based) definition. Model predictions agree quantitatively with experimental conformation and titration measurements, which support use of the model in the investigation of equilibrium solution properties of GAGs.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Massachusetts Institute of Technology. Department of Mechanical Engineering
Bathe, Mark, Gregory C. Rutledge, Alan J. Grodzinsky, and Bruce Tidor. "A Coarse-Grained Molecular Model for Glycosaminoglycans: Application to Chondroitin, Chondroitin Sulfate, and Hyaluronic Acid." Biophysical Journal Biophysical Journal Volume 88, Issue 6, June 2005: 3870–3887. © 2005 The Biophysical Society
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