Carbohydrate structure: the rocky road to automation
Carbohydrate structure: the rocky road to automation
复制标题
DOI：
10.1016/j.sbi.2016.11.011
复制
发表时间：
2017-06-01
影响因子：
6.8
通讯作者：
Cowtan, Kevin D.
中科院分区：
文献类型：
--
作者：
Agirre, Jon;Davies, Gideon J.;Cowtan, Kevin D.
随着直观的图形软件的引入，不是晶体学专家的结构生物学家现在能够快速建立完整的蛋白质或核酸模型。相比之下，碳水化合物处于完全不同的情况：存在很少的自动化，人工构建的尝试有时会被不正确的字典或改进问题所推翻。糖是立体化学最复杂的生物分子家族，作为吡喃糖环，具有明确的构象偏好。尽管如此，所有的细化程序都可以在没有任何电子密度支持的情况下产生中低分辨率的高能构象。这个问题使得受影响的结构在糖化学术语中无法使用。将结构糖生物学提高到“蛋白质标准”将需要对方法进行全面改革。时间是至关重要的，因为这个群体正在稳步提高糖蛋白的生产速度，而电子冷冻显微镜刚刚开始在晶体学方法最不可靠的分辨率范围内对糖蛋白进行精确成像。
With the introduction of intuitive graphical software, structural biologists who are not experts in crystallography are now able to build complete protein or nucleic acid models rapidly. In contrast, carbohydrates are in a wholly different situation: scant automation exists,, with manual building attempts being sometimes toppled by incorrect dictionaries or refinement problems. Sugars are the most stereochemically complex family of biomolecules and, as pyranose rings, have clear conformational preferences. Despite this, all refinement programs may produce high-energy conformations at medium to low resolution, without any support from the electron density. This problem renders the affected structures unusable in glyco-chemical terms. Bringing structural glycobiology up to 'protein standards' will require a total overhaul of the methodology. Time is of the essence, as the community is steadily increasing the production rate of glycoproteins, and electron cryomicroscopy has just started to image them in precisely that resolution range where crystallographic methods falter most.