The use of in silico strategies to develop the structural basis for a rational optimization of glycan-protein interactions remains a great challenge. This problem derives, in part, from the lack of technologies to quantitatively and qualitatively assess the complex assembling between a glycan and the targeted protein molecule. Since there is an unmet need for developing new sugar-targeted therapeutics, many investigators are searching for technology platforms to elucidate various types of molecular interactions within glycan-protein complexes and aid in the development of glycan-targeted therapies. Here we discuss three important technology platforms commonly used in the assessment of the complex assembly of glycosylated biomolecules, such as glycoproteins or glycosphingolipids: Biacore analysis, molecular docking, and molecular dynamics simulations. We will also discuss the structural investigation of glycosylated biomolecules, including conformational changes of glycans and their impact on molecular interactions within the glycan-protein complex. For glycoproteins, secreted protein acidic and rich in cysteine (SPARC), which is associated with various lung disorders, such as chronic obstructive pulmonary disease (COPD) and lung cancer, will be taken as an example showing that the core fucosylation of N-glycan in SPARC regulates protein-binding affinity with extracellular matrix collagen. For glycosphingolipids (GSLs), Globo H ceramide, an important tumor-associated GSL which is being actively investigated as a target for new cancer immunotherapies, will be used to demonstrate how glycan structure plays a significant role in enhancing angiogenesis in tumor microenvironments.

中文翻译：

---

剖析聚糖的构象及其与蛋白质的相互作用。

使用计算机模拟策略来开发结构基础以合理优化聚糖-蛋白质相互作用仍然是一个巨大的挑战。该问题部分是由于缺乏定量和定性评估聚糖与目标蛋白分子之间复杂组装的技术而引起的。由于开发新的以糖为靶标的治疗药物的需求尚未得到满足，因此许多研究人员正在寻找技术平台，以阐明聚糖-蛋白复合物中各种类型的分子相互作用，并协助开发以糖为靶标的治疗方法。在这里，我们讨论了通常用于评估糖基化生物分子（例如糖蛋白或鞘糖脂）的复杂装配的三个重要技术平台：Biacore分析，分子对接，和分子动力学模拟。我们还将讨论糖基化生物分子的结构研究，包括聚糖的构象变化及其对聚糖-蛋白质复合体内分子相互作用的影响。对于糖蛋白，以酸性蛋白和富含半胱氨酸（SPARC）的分泌蛋白为例，该蛋白与各种肺部疾病（例如慢性阻塞性肺疾病（COPD）和肺癌）有关，将显示N-聚糖的核心岩藻糖基化SPARC中的蛋白调节与细胞外基质胶原蛋白的蛋白结合亲和力。对于糖鞘脂（GSL），Globo H神经酰胺是一种重要的与肿瘤相关的GSL，正在积极研究其作为新型癌症免疫疗法的靶标，