Sadreyev Ruslan I, Kim Bong-Hyun, Grishin Nick V
Howard Hughes Medical Institute, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA.
Curr Opin Struct Biol. 2009 Jun;19(3):321-8. doi: 10.1016/j.sbi.2009.04.009. Epub 2009 May 29.
Recently, the nature of protein structure space has been widely discussed in the literature. The traditional discrete view of protein universe as a set of separate folds has been criticized in the light of growing evidence that almost any arrangement of secondary structures is possible and the whole protein space can be traversed through a path of similar structures. Here we argue that the discrete and continuous descriptions are not mutually exclusive, but complementary: the space is largely discrete in evolutionary sense, but continuous geometrically when purely structural similarities are quantified. Evolutionary connections are mainly confined to separate structural prototypes corresponding to folds as islands of structural stability, with few remaining traceable links between the islands. However, for a geometric similarity measure, it is usually possible to find a reasonable cutoff that yields paths connecting any two structures through intermediates.
最近，蛋白质结构空间的本质在文献中得到了广泛讨论。传统上认为蛋白质世界是由一组独立折叠组成的离散观点，鉴于越来越多的证据表明几乎任何二级结构的排列都是可能的，并且整个蛋白质空间可以通过相似结构的路径遍历，因此受到了批评。在这里，我们认为离散和连续描述并非相互排斥，而是相互补充的：从进化意义上讲，空间在很大程度上是离散的，但当纯粹的结构相似性被量化时，在几何上是连续的。进化联系主要局限于与作为结构稳定性孤岛的折叠相对应的独立结构原型，孤岛之间几乎没有可追溯的联系。然而，对于几何相似性度量，通常可以找到一个合理的截止值，该截止值能够产生通过中间体连接任何两个结构的路径。
