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A Coarse-Grained Molecular Model for Glycosaminoglycans: Application to Chondroitin, Chondroitin Sulfate, and Hyaluronic Acid

Mark Bathe ^* , Gregory C. Rutledge , Alan J. Grodzinsky ^*   and Bruce Tidor  

^* Departments of Mechanical Engineering, Chemical Engineering, Electrical Engineering and Computer Science, and the Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts

Correspondence: Address reprint requests to Bruce Tidor, Massachusetts Institute of Technology, Biological Engineering Division and Dept. of Electrical Engineering and Computer Science, Room 32-212, Cambridge, MA 02139. Tel.: 617-253-7258; E-mail: tidor{at}mit.edu.

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.

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				M. Bathe, G. C. Rutledge, A. J. Grodzinsky, and B. Tidor Osmotic Pressure of Aqueous Chondroitin Sulfate Solution: A Molecular Modeling Investigation Biophys. J., October 1, 2005; 89(4): 2357 - 2371. [Abstract] [Full Text] [PDF]