Path-based approach to random walks on networks characterizes how proteins evolve new functions.
Path-based approach to random walks on networks characterizes how proteins evolve new functions.
复制标题
基于路径的网络随机游走方法描述了蛋白质如何进化新功能。
DOI：
10.1103/physrevlett.111.088102
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发表时间：
2013
影响因子：
8.6
通讯作者：
Morozov,AlexandreV
中科院分区：
文献类型：
--
作者：
Manhart,Michael;Morozov,AlexandreV
我们开发了一种基于路径的方法，在具有任意加权边缘的网络上进行连续时间随机游走。我们描述了一种用于计算随机路径系综统计特性的有效数值算法。在展示了我们对两个反应速率问题的方法之后，我们提出了一个生物物理模型，该模型描述了蛋白质如何在保持热<？形式？>动态稳定性的同时进化出新功能。我们使用我们的方法来表征进化适应的动态，重现定向进化实验中观察到的几个关键特征。我们发现蛋白质通常分为两种性质不同的适应机制，具体取决于它们的结合和折叠能量。
We develop a path-based approach to continuous-time random walks on networks with arbitrarily weighted edges. We describe an efficient numerical algorithm for calculating statistical properties of the stochastic path ensemble. After demonstrating our approach on two reaction rate problems, we present a biophysical model that describes how proteins evolve new functions while maintaining thermo<?format ?>dynamic stability. We use our methodology to characterize dynamics of evolutionary adaptation, reproducing several key features observed in directed evolution experiments. We find that proteins generally fall into two qualitatively different regimes of adaptation depending on their binding and folding energetics.