BIOPHYSICAL THEORY AND MODELING |
A coarse-grained molecular model for glycosaminoglycans: Application to chondroitin, condroitin sulfate, and hyaluronic acid
Mark Bathe 1, Gregory C. Rutledge 1, Alan J. Grodzinsky 1 and Bruce Tidor 1*
1 Massachusetts Institute of Technology
* To whom correspondence should be addressed. E-mail: tidor{at}mit.edu.
Submitted on January 1, 2005
Revised on January 27, 2005
Accepted on 23 March 2005
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Abstract |
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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 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. Whereas 4-sulfation of the N-acetyl-Dgalactosamine 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 (worm-like-chain-based) and a microscopic (bond-vector-correlation-based) definition. Model predictions agree quantitatively with experimental conformation and titration measurements, which supports use of the model in the investigation of equilibrium solution properties of GAGs.
Key Words:
Metropolis Monte Carlo, coarse-graining, glycosaminoglycan, polyelectrolyte, proteoglycan, titration
