Department of Physics and Research Institute of Natural Science, Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Korea.
Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Waknaghat, Solan 173234, India.
Int J Mol Sci. 2020 Jun 29;21(13):4602. doi: 10.3390/ijms21134602.
Hyaluronic acid (HA) has a wide range of biomedical applications including the formation of hydrogels, microspheres, sponges, and films. The modeling of HA to understand its behavior and interaction with other biomolecules at the atomic level is of considerable interest. The atomistic representation of long HA polymers for the study of the macroscopic structural formation and its interactions with other polyelectrolytes is computationally demanding. To overcome this limitation, we developed a coarse grained (CG) model for HA adapting the Martini scheme. A very good agreement was observed between the CG model and all-atom simulations for both local (bonded interactions) and global properties (end-to-end distance, a radius of gyration, RMSD). Our CG model successfully demonstrated the formation of HA gel and its structural changes at high salt concentrations. We found that the main role of CaCl is screening the electrostatic repulsion between chains. HA gel did not collapse even at high CaCl concentrations, and the osmotic pressure decreased, which agrees well with the experimental results. This is a distinct property of HA from other proteins or polynucleic acids which ensures the validity of our CG model. Our HA CG model is compatible with other CG biomolecular models developed under the Martini scheme, which allows for large-scale simulations of various HA-based complex systems.
透明质酸（HA）在生物医学领域有广泛的应用，包括水凝胶、微球、海绵和薄膜的形成。对 HA 的建模，以了解其在原子水平上的行为和与其他生物分子的相互作用，具有相当大的意义。为了研究宏观结构形成及其与其他聚电解质的相互作用，需要对长链 HA 聚合物进行原子级的描述，这在计算上是具有挑战性的。为了克服这一限制，我们根据 Martini 方案开发了一种用于 HA 的粗粒化（CG）模型。该 CG 模型与全原子模拟在局部（键相互作用）和全局性质（末端到末端的距离、回转半径、均方根偏差）方面都非常吻合。我们的 CG 模型成功地演示了 HA 凝胶的形成及其在高盐浓度下的结构变化。我们发现，CaCl 的主要作用是屏蔽链之间的静电排斥。即使在高浓度的 CaCl 下，HA 凝胶也不会崩溃，渗透压降低，这与实验结果非常吻合。这是 HA 与其他蛋白质或多核苷酸的显著区别，保证了我们 CG 模型的有效性。我们的 HA CG 模型与 Martini 方案下开发的其他 CG 生物分子模型兼容，这允许对各种基于 HA 的复杂系统进行大规模模拟。
