Exploring residue component contributions to dynamical network models of allostery.
Exploring residue component contributions to dynamical network models of allostery.
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DOI：
10.1021/ct300377a
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发表时间：
2012-08-14
影响因子：
5.5
通讯作者：
Amaro, Rommie E.
中科院分区：
文献类型：
--
作者：
VanWart, Adam T.;Eargle, John;Luthey-Schulten, Zaida;Amaro, Rommie E.
生物系统中的变构调节是相当感兴趣的，因为有大量的蛋白质表现出这种行为。从分子动力学模拟中获得的网络模型已被证明是分析变构的有力工具。在这项工作中，不同的粗粒残基表示（节点）一起使用的动态网络模型来研究模型的变构调节。该模型假设变构信号依赖于蛋白质取代基的位置相关性，如通过分子动力学模拟确定的，并使用相关运动来生成两个给定节点之间的信号权重。我们使用笛卡尔坐标中的不同节点表示来研究四种类型的网络模型：（i）残留α-碳，（ii）侧链质心，（iii）骨架质心和整个（iv）残留质心。所有相关性都由动态联系人映射过滤，该映射根据物理接近度定义节点之间允许的交互。我们将这四种模型应用于咪唑甘油磷酸合酶（IGPS），它提供了一个经过充分研究的实验框架，其中已知变构通信在不同的蛋白质结构域（例如蛋白质二聚体界面）中持续存在。IGPS被建模为节点和加权边的网络。使用加权网络的弗洛伊德Warshall算法追踪最佳变构途径，并使用Girvan-Newman算法进行群落分析（一种层次聚类形式）。我们的研究结果表明，动力学信息编码的残留物中心的质量必须被包括在内，以检测残留物，实验上已知发挥作用的变构通信IGPS。更广泛地说，这种新方法可能是有用的预测途径的变构通信的任何生物分子系统的原子细节。
Allosteric regulation in biological systems is of considerable interest given the vast number of proteins that exhibit such behavior. Network models obtained from molecular dynamics simulations have been shown to be powerful tools for the analysis of allostery. In this work, different coarse-grain residue representations (nodes) are used together with a dynamical network model to investigate models of allosteric regulation. This model assumes that allosteric signals are dependent on positional correlations of protein substituents, as determined through molecular dynamics simulations, and uses correlated motion to generate a signaling weight between two given nodes. We examine four types of network models using different node representations in Cartesian coordinates: the (i) residue alpha-carbons, (ii) sidechain center of mass, (iii) backbone center of mass, and the entire (iv) residue center of mass. All correlations are filtered by a dynamic contact map that defines the allowable interactions between nodes based on physical proximity. We apply the four models to imidazole glycerol phosphate synthase (IGPS), which provides a well-studied experimental framework in which allosteric communication is known to persist across disparate protein domains (e.g. a protein dimer interface). IGPS is modeled as a network of nodes and weighted edges. Optimal allosteric pathways are traced using the Floyd Warshall algorithm for weighted networks, and community analysis (a form of hierarchical clustering) is performed using the Girvan-Newman algorithm. Our results show that dynamical information encoded in the residue center of mass must be included in order to detect residues that are experimentally known to play a role in allosteric communication for IGPS. More broadly, this new method may be useful for predicting pathways of allosteric communication for any biomolecular system in atomic detail.
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影响因子：
4.4
作者：
Andricioaei, I;Karplus, M
通讯作者：
Karplus, M
DOI：
10.1073/pnas.1331150100
发表时间：
2003-06-24
影响因子：
11.1
作者：
Amaro, R;Tajkhorshid, E;Luthey-Schulten, Z
通讯作者：
Luthey-Schulten, Z
影响因子：
3.4
作者：
Amaro, RE;Myers, RS;Luthey-Schulten, ZA
通讯作者：
Luthey-Schulten, ZA
影响因子：
--
作者：
Chennubhotla, Chakra;Yang, Zheng;Bahar, Ivet
通讯作者：
Bahar, Ivet
影响因子：
5.6
作者：
Bradley, Michael J.;Chivers, Peter T.;Baker, Nathan A.
通讯作者：
Baker, Nathan A.