College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Department of Chemistry, Princeton University, Princeton, NJ, United States of America.
PLoS Comput Biol. 2018 Dec 3;14(12):e1006393. doi: 10.1371/journal.pcbi.1006393. eCollection 2018 Dec.
Intrinsically disordered proteins/regions (IDPs/IDRs) are prevalent in allosteric regulation. It was previously thought that intrinsic disorder is favorable for maximizing the allosteric coupling. Here, we propose a comprehensive ensemble model to compare the roles of both order-order transition and disorder-order transition in allosteric effect. It is revealed that the MWC pathway (order-order transition) has a higher probability than the EAM pathway (disorder-order transition) in allostery, suggesting a complicated role of IDPs/IDRs in regulatory proteins. In addition, an analytic formula for the maximal allosteric coupling response is obtained, which shows that too stable or too unstable state is unfavorable to endow allostery, and is thus helpful for rational design of allosteric drugs.
无规蛋白/区域（IDPs/IDRs）在变构调节中普遍存在。以前认为，固有无序有利于最大程度地增加变构偶联。在这里，我们提出了一个综合的集合模型来比较有序-无序转变和无序-有序转变在变构效应中的作用。结果表明，在变构作用中，MWC 途径（有序-有序转变）比 EAM 途径（无序-有序转变）具有更高的概率，这表明 IDPs/IDRs 在调节蛋白中具有复杂的作用。此外，还获得了最大变构偶联响应的解析公式，该公式表明，太稳定或太不稳定的状态不利于赋予变构性，因此有助于合理设计变构药物。
