Heparin/heparan sulfates (H/HS) are ubiquitous biopolymers that interact with many proteins to induce a range of biological functions. Unfortunately, how these biopolymers recognize their preferred protein targets remain poorly understood. It is suggested that computational simulations offer attractive avenues but a number of challenges, e.g., difficulty of selecting a comprehensive force field, few simple tools to interpret data, among others, remain. This work addresses several such challenges so as to help ease the implementation and analysis of computational experiments. First, this work presents a rigorous comparison of two different recent force fields, CHARMM36 and GLYCAM06, for H/HS studies. Second, it introduces two new straightforward parameters, i.e., end-to-end distance and minimum volume enclosing ellipsoid, to understand the myriad conformational forms of oligosaccharides that evolve over time in water. Third, it presents an application to elucidate the number and nature of inter and intramolecular, nondirect bridging water molecules, which help stabilize unique forms of H/HS. The results show that nonspecialists can use either CHARMM36 or GLYCAM06 force fields because both gave comparable results, albeit with small differences. The comparative study shows that the HS hexasaccharide samples a range of conformations with nearly equivalent energies, which could be the reason for its recognition by different proteins. Finally, analysis of the nondirect water bridges across the dynamics trajectory shows their importance in stabilization of certain conformational forms, which may become important for protein recognition. Overall, the work aids nonspecialists employ computational studies for understanding the solution behavior of H/HS.

中文翻译：

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使用简单的新工具对游离溶液糖胺聚糖动力学进行严格分析。

肝素/硫酸乙酰肝素 (H/HS) 是无处不在的生物聚合物，可与许多蛋白质相互作用以诱导一系列生物功能。不幸的是，这些生物聚合物如何识别其首选的蛋白质靶标仍然知之甚少。有人建议，计算模拟提供了有吸引力的途径，但仍然存在许多挑战，例如，选择综合力场的困难，解释数据的简单工具很少，等等。这项工作解决了几个这样的挑战，以帮助简化计算实验的实施和分析。首先，这项工作对 H/HS 研究的两个不同的近期力场 CHARMM36 和 GLYCAM06 进行了严格的比较。其次，它引入了两个新的直接参数，即端到端距离和包围椭球的最小体积，了解在水中随时间演变的寡糖的无数构象形式。第三，它提出了一个应用来阐明分子间和分子内非直接桥接水分子的数量和性质，这有助于稳定独特形式的 H/HS。结果表明，非专业人士可以使用 CHARMM36 或 GLYCAM06 力场，因为两者都给出了可比较的结果，尽管差异很小。对比研究表明，HS 六糖对一系列具有几乎相同能量的构象进行采样，这可能是其被不同蛋白质识别的原因。最后，对跨动力学轨迹的非直接水桥的分析表明它们在稳定某些构象形式方面的重要性，这可能对蛋白质识别变得重要。总体，