Network theory methods and molecular dynamics (MD) simulations are accepted tools to study allosteric regulation. Indeed, dynamic networks built upon correlation analysis of MD trajectories provide detailed information about communication paths between distant sites. In this context, we aimed to understand whether the efficiency of intramolecular communication could be used to predict the allosteric potential of a given site. To this end, we performed MD simulations and network theory analyses in cathepsin K (catK), whose allosteric sites are well defined. To obtain a quantitative measure of the efficiency of communication, we designed a new protocol that enables the comparison between properties related to ensembles of communication paths obtained from different sites. Further, we applied our strategy to evaluate the allosteric potential of different catK cavities not yet considered for drug design. Our predictions of the allosteric potential based on intramolecular communication correlate well with previous catK experimental and theoretical data. We also discuss the possibility of applying our approach to other proteins from the same family.

中文翻译：

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基于分子内通讯鉴定组织蛋白酶K中潜在的变构结合位点。

网络理论方法和分子动力学（MD）模拟是研究变构调控的公认工具。实际上，基于MD轨迹的相关性分析建立的动态网络提供了有关远程站点之间通信路径的详细信息。在这种情况下，我们旨在了解分子内通讯的效率是否可用于预测给定部位的变构潜力。为此，我们在组织蛋白酶K（catK）中进行了MD模拟和网络理论分析，其构象部位明确定义。为了获得通信效率的定量度量，我们设计了一种新协议，该协议可以对与从不同站点获得的通信路径集合相关的属性进行比较。进一步，我们应用我们的策略来评估尚未用于药物设计的不同catK腔的变构潜力。我们基于分子内通讯对变构潜力的预测与先前的catK实验和理论数据有很好的关联。我们还将讨论将我们的方法应用于同一家族的其他蛋白质的可能性。