Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 Helsinki, Finland.
J Comput Chem. 2010 Jun;31(8):1670-80. doi: 10.1002/jcc.21453.
Chondroitin-6-sulfate (C6S) is a glycosaminoglycan (GAG) constituent in the extracellular matrix, which participates actively in crucial biological processes, as well as in various pathological conditions, such as atherosclerosis and cancer. Molecular interactions involving the C6S chain are therefore of considerable interest. A computational model for atomistic simulation was built. This work describes the design and validation of a force field for a C6S dodecasaccharide chain. The results of an extensive molecular dynamics simulation performed with the new force field provide a novel insight into the structure and dynamics of the C6S chain. The intramolecular H-bonds in the disaccharide linkage region are suggested to play a major role in determining the chain structural dynamics. Moreover, the unravelling of an additional H-bond involving the sulfate groups in C6S is interesting as changes in sulfation have been claimed to be an important factor in several diseases. The force field will prove useful for future studies of crucial interactions between C6S and various nanoassemblies. It can also be used as a basis for modeling of other GAGs.
硫酸软骨素-6-硫酸盐（C6S）是细胞外基质中糖胺聚糖（GAG）的组成部分，它积极参与关键的生物过程以及各种病理状况，如动脉粥样硬化和癌症。因此，涉及 C6S 链的分子相互作用具有相当大的意义。建立了用于原子模拟的计算模型。这项工作描述了用于 C6S 十二糖链的力场的设计和验证。使用新力场进行的广泛分子动力学模拟的结果提供了对 C6S 链结构和动力学的新见解。建议在二糖键合区域的分子内氢键在确定链结构动力学中起主要作用。此外，解开涉及 C6S 中硫酸盐基团的额外氢键很有趣，因为据称硫酸化的变化是几种疾病的重要因素。该力场将有助于研究 C6S 与各种纳米组装体之间的关键相互作用的未来研究。它也可以用作建模其他 GAG 的基础。
