“F1000（Faculty of 1000 Medicine）”又名“千名医学家”，是由美国哈佛大学和英国剑桥大学等全世界2500名国际顶级医学教授组成的国际权威机构。1月，F1000上的两篇论文引发了关于在无稳定结构的情况下，是否能进行蛋白识别的争论。
蛋白质结构是三维的空间结构，在去折叠态时，蛋白质链上相距较远的氨基酸残基之间的物理相互作用较少，在折叠态时，则存在很多这样的长程特异相互作用，它们实际上定义了蛋白质的三级结构。所谓蛋白质结构主要是针对这种长程的特异相互作用而言。它们本质上是三维空间中原子和原子基团的相对位置和取向，测定蛋白质的空间结构就是要通过物（化学）手段确定这些相对位置和取向。
然而对于譬如酶作用等方面的蛋白识别机理而言，仍然存在一些谜题有待解决，这两篇文章提出了两种不同的观点，有助于解析这些问题。
在第一篇文章：“The case for intrinsically disordered proteins playing contributory roles in molecular recognition without a stable 3D structure”中，来自印第安纳大学医学院的Keith Dunker和俄罗斯科学院的Vladimir N. Uversky提出，蛋白识别的锁钥模型并不是一个普遍原理——锁钥模型认为酶和底物的关系如同锁和钥匙的关系一样，酶分子就像一把锁，而底物像是一把钥匙，当酶和底物的空间构象正好能完全弥合的时候，才能像钥匙把锁打开一样，产生相互作用。而这项研究的研究人员则认为一些蛋白即使没有一种严格的结构，比如天然失序蛋白（IDPs）也具有功能。
相反，第二篇文章（Protein flexibility, not disorder, is intrinsic to molecular recognition）则认为，机体细胞中真实环境下的蛋白功能依赖于其结构，并且蛋白识别需要能相互识别结合的互补结构。
而且文章作者：巴黎第十一大学的Jo?l Janin，和伦敦帝国学院的Michael J.E. Sternberg还指出，许多蛋白在试管中看起来好似是无序的，但是实际上，这些蛋白如果和伴体（PWPs）相结合，就能与细胞中其它元件相互作用，形成有序结构，行使功能。
对于这一观点，第一篇文章的作者Dunker和 Uversky反驳道，普通蛋白和无序蛋白IDPs之间的主要差别，在于前者先折叠后结合到伴体上，而后者则是与伴体结合后才改变其无序的状态。而且比较于“等待伴体”，一些IDPs活动性更强，能从一种伴体转向另外一种，并在改变伴体的时候，改变其结构。
MRC实验室的Richard Henderson对这两篇文章进行了点评，他表示，“这两篇文章都提出了关于看似天然无序的蛋白功能的一些观点，他们有着不同的侧重点，这毫无疑问将促进结构生物学研究实验和争论的更深入发展。时间将会告诉我们，哪种，或者哪几种模型才是大自然真实的做法。”(生物谷Bioon.com)
doi: 10.3410/B5-2
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Protein flexibility, not disorder, is intrinsic to molecular recognition
Joël Janin1 and Michael J.E. Sternberg2
An ‘intrinsically disordered protein’ (IDP) is assumed to be unfolded in the cell and perform its biological function in that state. We contend that most intrinsically disordered proteins are in fact proteins waiting for a partner (PWPs), parts of a multi-component complex that do not fold correctly in the absence of other components. Flexibility, not disorder, is an intrinsic property of proteins, exemplified by X-ray structures of many enzymes and protein-protein complexes. Disorder is often observed with purified proteins in vitro and sometimes also in crystals, where it is difficult to distinguish from flexibility. In the crowded environment of the cell, disorder is not compatible with the known mechanisms of protein-protein recognition, and, foremost, with its specificity. The self-assembly of multi-component complexes may, nevertheless, involve the specific recognition of nascent polypeptide chains that are incompletely folded, but then disorder is transient, and it must remain under the control of molecular chaperones and of the quality control apparatus that obviates the toxic effects it can have on the cell.
doi: 10.3410/B5-1
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The case for intrinsically disordered proteins playing contributory roles in molecular recognition without a stable 3D structure
Vladimir N. Uversky1,2 and A. Keith Dunker1
The classical ‘lock-and-key’ and ‘induced-fit’ mechanisms for binding both originated in attempts to explain features of enzyme catalysis. For both of these mechanisms and for their recent refinements, enzyme catalysis requires exquisite spatial and electronic complementarity between the substrate and the catalyst. Thus, binding models derived from models originally based on catalysis will be highly biased towards mechanisms that utilize structural complementarity. If mere binding without catalysis is the endpoint, then the structural requirements for the interaction become much more relaxed. Recent observations on specific examples suggest that this relaxation can reach an extreme lack of specific 3D structure, leading to molecular recognition with biological consequences that depend not only upon structural and electrostatic complementarity between the binding partners but also upon kinetic, entropic, and generalized electrostatic effects. In addition to this discussion of binding without fixed structure, examples in which unstructured regions carry out important biological functions not involving molecular recognition will also be discussed. Finally, we discuss whether ‘intrinsically disordered protein’ (IDP) represents a useful new concept.
