National University of Singapore, Department of Biological Sciences, 14 Science Drive 4, Singapore 117543, Singapore.
Bioinformatics Institute (A*STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore.
J Chem Theory Comput. 2024 Apr 23;20(8):3308-3321. doi: 10.1021/acs.jctc.3c01088. Epub 2024 Feb 15.
Proteoglycans contain glycosaminoglycans (GAGs) which are negatively charged linear polymers made of repeating disaccharide units of uronic acid and hexosamine units. They play vital roles in numerous physiological and pathological processes, particularly in governing cellular communication and attachment. Depending on their sulfonation state, acetylation, and glycosidic linkages, GAGs belong to different families. The high molecular weight, heterogeneity, and flexibility of GAGs hamper their characterization at atomic resolution, but this may be circumvented via coarse-grained (CG) approaches. In this work, we report a CG model for a library of common GAG types in their isolated or proteoglycan-linked states compatible with version 2.2 (v2.2) of the widely popular CG Martini force field. The model reproduces conformational and thermodynamic properties for a wide variety of GAGs, as well as matching structural and binding data for selected proteoglycan test systems. The parameters developed here may thus be employed to study a range of GAG-containing biomolecular systems, thereby benefiting from the efficiency and broad applicability of the Martini framework.
蛋白聚糖含有糖胺聚糖（GAGs），这是一种由重复的二糖单位组成的带负电荷的线性聚合物，由糖醛酸和己糖胺单位组成。它们在许多生理和病理过程中起着至关重要的作用，特别是在调节细胞通讯和附着方面。根据它们的磺化状态、乙酰化和糖苷键合，GAGs 属于不同的家族。GAGs 的高分子量、异质性和灵活性阻碍了它们在原子分辨率下的特性描述，但可以通过粗粒化（CG）方法来解决。在这项工作中，我们报告了一个 CG 模型库，其中包含常见的 GAG 类型，它们处于分离或与蛋白聚糖连接的状态，与广泛使用的 CG Martini 力场的版本 2.2（v2.2）兼容。该模型再现了各种 GAG 的构象和热力学性质，以及为选定的蛋白聚糖测试系统匹配的结构和结合数据。因此，这里开发的参数可用于研究一系列含有 GAG 的生物分子系统，从而受益于 Martini 框架的效率和广泛适用性。
