Ensemble-Biased Metadynamics: A Molecular Simulation Method to Sample Experimental Distributions
Ensemble-Biased Metadynamics: A Molecular Simulation Method to Sample Experimental Distributions
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DOI：
10.1016/j.bpj.2015.05.024
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发表时间：
2015-06-16
影响因子：
3.4
通讯作者：
Faraldo-Gomez, Jose D.
中科院分区：
文献类型：
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作者：
Marinelli, Fabrizio;Faraldo-Gomez, Jose D.
我们介绍了一种用于分子动力学(MD)模拟的增强型抽样方法，称为系综偏向元动力学(EBMetaD)。该方法偏向于传统的MD模拟，以采样与一个或多个先验已知的概率分布一致的分子系综，例如，通过双电子-电子共振或其他光谱技术获得的实验分子内距离分布。为此，EBMetaD在整个模拟过程中增加了自适应偏置潜力，以阻止对与目标概率分布不一致的配置进行采样。引入的偏差是满足目标分布所需的最小偏差，即EBMetaD满足最大熵原理。与其他方法不同，EBMetaD不需要多个模拟副本，也不需要引入拉格朗日乘子，因此在计算上是高效的，在实践中也是直接的。我们展示了该方法在模型系统和显性水中的自旋标记T4溶菌酶中的性能和准确性，并展示了EBMetaD如何在几十纳秒的模拟时间内同时再现三个双电子-电子共振距离分布。EBMetaD集成在开源羽化插件(www.pluled-code.org)中，因此可以很容易地与多个MD引擎一起使用。
We introduce an enhanced-sampling method for molecular dynamics (MD) simulations referred to as ensemble-biased metadynamics (EBMetaD). The method biases a conventional MD simulation to sample a molecular ensemble that is consistent with one or more probability distributions known a priori, e.g., experimental intramolecular distance distributions obtained by double electron-electron resonance or other spectroscopic techniques. To this end, EBMetaD adds an adaptive biasing potential throughout the simulation that discourages sampling of configurations inconsistent with the target probability distributions. The bias introduced is the minimum necessary to fulfill the target distributions, i.e., EBMetaD satisfies the maximum-entropy principle. Unlike other methods, EBMetaD does not require multiple simulation replicas or the introduction of Lagrange multipliers, and is therefore computationally efficient and straightforward in practice. We demonstrate the performance and accuracy of the method for a model system as well as for spin-labeled T4 lysozyme in explicit water, and show how EBMetaD reproduces three double electron-electron resonance distance distributions concurrently within a few tens of nanoseconds of simulation time. EBMetaD is integrated in the open-source PLUMED plug-in (www.plumed-code.org), and can be therefore readily used with multiple MD engines.