Molecular Dynamics Simulations of Chondroitin Sulfate in Explicit Solvent: Point Charge Water Models Compared

Sulfated glycosaminoglycans (GAGs) are an important class of biomacromolecules involved in many biological functions. Due to the inherent limitations of experimental techniques in assessing the aspects related to their dynamics and interactions in solution, theoretical approaches like molecular dynamics simulations found extended applicability in complementing the experimental field. Recognizing the importance of the accurate solvent representation in carbohydrate simulations in explicit solvent, in this work we have tested four popular water models, namely TIP3P, TIP4P, TIP4P-EW and TIP5P, with respect to their influence on the conformation of a model chondroitin sulfate octasaccharide. The conformation adopted by the simulated saccharide showed no dependency on the water model used on the (1-4) glycosidc linkage type, while in the case of (1-3) linkage detectable differences were noticed. In general, it was found that TIP3P favors the direct intra-molecular hydrogen bonding of chondroitin sulfate, while the 4-site and 5-site models disfavor it, facilitating in turn water mediated bridges. Taking into consideration not only the accuracy of the models, but also the computational cost, the data presented here suggest that the TIP4P and TIP4P-EW models give the optimum quality/performance balance.