Proteins in their native states can be represented as ensembles of conformers in dynamical equilibrium. Thermal fluctuations are responsible for transitions between these conformers. Normal-modes analysis (NMA) using elastic network models (ENMs) provides an efficient procedure to explore global dynamics of proteins commonly associated with conformational transitions. In the present work, we present an iterative approach to explore protein conformational spaces by introducing structural distortions according to their equilibrium dynamics at room temperature. The approach can be used either to perform unbiased explorations of conformational space or to explore guided pathways connecting two different conformations, e.g., apo and holo forms. In order to test its performance, four proteins with different magnitudes of structural distortions upon ligand binding have been tested. In all cases, the conformational selection model has been confirmed and the conformational space between apo and holo forms has been encompassed. Different strategies have been tested that impact on the efficiency either to achieve a desired conformational change or to achieve a balanced exploration of the protein conformational multiplicity.

中文翻译：

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通过正常模式分析获得的热涨落来探索构象空间。

处于天然状态的蛋白质可以表示为动态平衡中的构象体集合。温度波动是这些构象异构体之间过渡的原因。使用弹性网络模型（ENM）的正常模式分析（NMA）提供了一种有效的程序来探索通常与构象转变有关的蛋白质的整体动力学。在当前的工作中，我们提出了一种迭代方法，通过根据室温下的平衡动力学引入结构畸变来探索蛋白质构象空间。该方法既可以用于进行构象空间的无偏探索，也可以用于探索连接两个不同构象（例如载脂蛋白和全脂蛋白形式）的引导途径。为了测试其性能，已经测试了四种在配体结合后具有不同大小的结构变形的蛋白质。在所有情况下，构象选择模型都已得到确认，并且载脂蛋白和整体形式之间的构象空间也已包含在内。已经测试了不同的策略，这些策略对实现所需构象变化或对蛋白质构象多样性的平衡探索具有影响。