Department of Medicinal Chemistry & Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, USA.
Department of Medicinal Chemistry & Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, USA.
Curr Opin Struct Biol. 2018 Jun;50:91-100. doi: 10.1016/j.sbi.2017.12.004. Epub 2018 Jan 9.
Glycosaminoglycans (GAGs) play key roles in virtually all biologic responses through their interaction with proteins. A major challenge in understanding these roles is their massive structural complexity. Computational approaches are extremely useful in navigating this bottleneck and, in some cases, the only avenue to gain comprehensive insight. We discuss the state-of-the-art on computational approaches and present a flowchart to help answer most basic, and some advanced, questions on GAG-protein interactions. For example, firstly, does my protein bind to GAGs?; secondly, where does the GAG bind?; thirdly, does my protein preferentially recognize a particular GAG type?; fourthly, what is the most optimal GAG chain length?; fifthly, what is the structure of the most favored GAG sequence?; and finally, is my GAG-protein system 'specific', 'non-specific', or a combination of both? Recent advances show the field is now poised to enable a non-computational researcher perform advanced experiments through the availability of various tools and online servers.
糖胺聚糖（GAGs）通过与蛋白质的相互作用，在几乎所有的生物反应中都起着关键作用。理解这些作用的主要挑战是它们巨大的结构复杂性。计算方法在克服这一瓶颈方面非常有用，在某些情况下，这是获得全面深入了解的唯一途径。我们讨论了计算方法的最新进展，并提出了一个流程图，以帮助回答关于 GAG-蛋白相互作用的最基本和一些高级问题。例如，首先，我的蛋白质是否与 GAGs 结合？其次，GAG 在哪里结合？第三，我的蛋白质是否优先识别特定的 GAG 类型？第四，最理想的 GAG 链长度是多少？第五，最受欢迎的 GAG 序列的结构是什么？最后，我的 GAG-蛋白系统是“特异性”、“非特异性”还是两者的组合？最近的进展表明，该领域现在已经准备好通过各种工具和在线服务器的可用性，使非计算研究人员能够进行高级实验。
