Improved model of hydrated calcium ion for molecular dynamics simulations using classical biomolecular force fields.
Improved model of hydrated calcium ion for molecular dynamics simulations using classical biomolecular force fields.
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DOI：
10.1002/bip.22868
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发表时间：
2016-10
期刊：
影响因子：
2.9
通讯作者：
Aksimentiev A
中科院分区：
文献类型：
--
作者：
Yoo J;Wilson J;Aksimentiev A
钙离子（Ca2+）在细胞信号传导和脑功能等多种基本生物过程中起着关键作用。分子动力学（MD）模拟已被用于研究这种相互作用，然而，由标准MD力场提供的Ca2+模型的准确性尚未经过严格测试。在这里，我们通过计算模型化合物的渗透压和DNA-DNA相互作用的自由能来评估来自最流行的经典力场AMBER和CHARMM的Ca2+模型的性能。在使用两种标准模型进行的模拟中，可以看到Ca2+离子与氯化物、醋酸盐和磷酸盐形成人工簇；CaAc2和CaCl2溶液的渗透压都是两个力场实验值的一小部分。在Ca2+介导的DNA -DNA相互作用的模拟中，使用Ca2+离子的标准参数化会导致定性错误的结果：AMBER和CHARMM模拟都表明DNA间有很强的吸引力，而在实验中，DNA分子相互排斥。Ca2+对DNA磷酸盐的人工吸引力足够强，可以影响电场驱动的DNA通过固态纳米孔易位的方向。为了解决标准Ca2+模型的这些缺点，我们引入了一个自定义的水合Ca2+离子模型，并表明使用我们的模型可以使上述MD模拟的结果与实验定量一致。我们改进的Ca2+模型可以很容易地应用于各种生物分子系统的MD模拟，包括核酸、蛋白质和脂质双层膜。
Calcium ions (Ca2+) play key roles in various fundamental biological processes such as cell signaling and brain function. Molecular dynamics (MD) simulations have been used to study such interactions, however, the accuracy of the Ca2+ models provided by the standard MD force fields has not been rigorously tested. Here, we assess the performance of the Ca2+ models from the most popular classical force fields AMBER and CHARMM by computing the osmotic pressure of model compounds and the free energy of DNA–DNA interactions. In the simulations performed using the two standard models, Ca2+ ions are seen to form artificial clusters with chloride, acetate, and phosphate species; the osmotic pressure of CaAc2 and CaCl2 solutions is a small fraction of the experimental values for both force fields. Using the standard parameterization of Ca2+ ions in the simulations of Ca2+-mediated DNA–DNA interactions leads to qualitatively wrong outcomes: both AMBER and CHARMM simulations suggest strong inter-DNA attraction whereas, in experiment, DNA molecules repel one another. The artificial attraction of Ca2+ to DNA phosphate is strong enough to affect the direction of the electric field-driven translocation of DNA through a solid-state nanopore. To address these shortcomings of the standard Ca2+ model, we introduce a custom model of a hydrated Ca2+ ion and show that using our model brings the results of the above MD simulations in quantitative agreement with experiment. Our improved model of Ca2+ can be readily applied to MD simulations of various biomolecular systems, including nucleic acids, proteins and lipid bilayer membranes.