Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics.
Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics.
复制标题
DOI：
10.1096/fj.11-190868
复制
发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Kleinjung J
中科院分区：
文献类型：
--
作者：
Pandini A;Fornili A;Fraternali F;Kleinjung J
变构提供了一种高度特异的方式来调节蛋白质的功能。因此，了解这一机制对蛋白质科学和药物开发具有重要意义。然而，变构信号的传递很难在实验上检测到，也很难模拟，因为它通常是由沿着多条路径传播的局部结构变化所介导的。为了解决这个问题，我们开发了一种方法，通过分子动力学模拟的信息理论分析来识别通信路径。信号传播被描述为通过相关的局部运动网络进行的信息交换，该网络被建模为蛋白质片段的正则状态之间的转换。该方法被用于描述双组分调控体系中的变构作用。特别是，从变构位点到受体结构域NTRC信号面的传递被证明是由一层中枢残基介导的。优先连接到变构中心的中心位置被发现与实验确定的参与信号传递的关键残基非常一致。与Chey和FixJ同系物网络的比较突出了他们在动力学上的相似之处。特别是，我们发现在所有三种蛋白质的非活性状态下，变构和功能位点之间的预先组织的片段连接网络已经存在。-Pandini，A.，Fornili，A.，Fraternali，F.，Kleinsung，J.通过蛋白质动力学的信息论分析检测变构信号的传递。
Allostery offers a highly specific way to modulate protein function. Therefore, understanding this mechanism is of increasing interest for protein science and drug discovery. However, allosteric signal transmission is difficult to detect experimentally and to model because it is often mediated by local structural changes propagating along multiple pathways. To address this, we developed a method to identify communication pathways by an information-theoretical analysis of molecular dynamics simulations. Signal propagation was described as information exchange through a network of correlated local motions, modeled as transitions between canonical states of protein fragments. The method was used to describe allostery in two-component regulatory systems. In particular, the transmission from the allosteric site to the signaling surface of the receiver domain NtrC was shown to be mediated by a layer of hub residues. The location of hubs preferentially connected to the allosteric site was found in close agreement with key residues experimentally identified as involved in the signal transmission. The comparison with the networks of the homologues CheY and FixJ highlighted similarities in their dynamics. In particular, we showed that a preorganized network of fragment connections between the allosteric and functional sites exists already in the inactive state of all three proteins.—Pandini, A., Fornili, A., Fraternali, F., Kleinjung, J. Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics.
登录
查看更多内容
DOI：
10.1016/j.str.2009.06.008
发表时间：
2009-08-12
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
del Sol A;Tsai CJ;Ma B;Nussinov R
通讯作者：
Nussinov R
影响因子：
2.9
作者：
Genoni, Alessandro;Morra, Giulia;Colombo, Giorgio
通讯作者：
Colombo, Giorgio
影响因子：
3.2
作者：
Appleby, JL;Bourret, RB
通讯作者：
Bourret, RB
影响因子：
2.9
作者：
Daily, Michael D.;Upadhyaya, Tarak J.;Gray, Jeffrey J.
通讯作者：
Gray, Jeffrey J.
影响因子：
2.4
作者：
Hess, B
通讯作者：
Hess, B