Magnesium Ion-Water Coordination and Exchange in Biomolecular Simulations
Magnesium Ion-Water Coordination and Exchange in Biomolecular Simulations
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DOI：
10.1021/ct3000734
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发表时间：
2012-04-01
影响因子：
5.5
通讯作者：
Villa, Alessandra
中科院分区：
文献类型：
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作者：
Allner, Olof;Nilsson, Lennart;Villa, Alessandra
镁离子在核糖核酸系统的结构和折叠机制中具有重要作用。为了正确地模拟这些生物物理过程，所应用的分子模型应该再现离子在水溶液中的动力学性质。在这里，我们已经研究了镁离子与水分子和核酸系统的结合动力学使用分子动力学模拟详细。我们已经验证了生物分子力场中使用的参数，如AMBER和CHARMM，用于Mg 2+离子以及生物相关离子Na+，K+和Ca 2+以及三种不同的水模型（TIP 3 P，SPC/E和TIPSP）。结果表明，Mg ~（2+）离子与Na ~+、K ~+和Ca ~（2+）离子的交换速率比Na ~+、K ~+和Ca ~（2+）离子的交换速率慢，与实验趋势一致，但无论力场和水模型如何，模拟值都比实验观测到的Mg ~（2+）-水交换速率低几个数量级。一组新的参数为Mg 2+的开发，以重现实验动力学数据。这一套也导致更好地再现结构数据比现有的模型。我们已经将新的参数集应用于Mg 2+与单磷酸模型系统的结合，并与嘌呤核糖开关，添加A-核糖开关。与Mg 2 +-水结果一致，新开发的参数显示出比所有其他模型更好地描述了Mg 2 +-磷酸盐结合的结构和动力学。离子结合到核糖开关系统的表征表明，新的参数集不影响核糖核酸系统的全局结构或参与直接或间接结合的离子的数量。观察到A-核糖开关和Mg 2+离子之间的水桥接触的数量略有减少。结果支持新开发的参数的能力，以提高动力学描述的Mg 2+和磷酸根离子和它们的核酸模拟的适用性。
Magnesium ions have an important role in the structure and folding mechanism of ribonucleic acid systems. To properly simulate these biophysical processes, the applied molecular models should reproduce, among other things, the kinetic properties of the ions in water solution. Here, we have studied the kinetics of the binding of magnesium ions with water molecules and nucleic acid systems using molecular dynamics simulation in detail. We have validated the parameters used in biomolecular force fields, such as AMBER and CHARMM, for Mg2+ ions and also for the biologically relevant ions Na+, K+ and Ca2+ together with three different water models (TIP3P, SPC/E, and TIPSP). The results show that Mg2+ ions have a slower exchange rate than Na+, K+ and Ca2+ in agreement with the experimental trend, but the simulated value underestimates the experimentally observed Mg2+-water exchange rate by several orders of magnitude, irrespective of the force field and water model. A new set of parameters for Mg2+ was developed to reproduce the experimental kinetic data. This set also leads to better reproduction of structural data than existing models. We have applied the new parameter set to Mg2+ binding with a monophosphate model system and with the purine riboswitch, add A-riboswitch. In line with the Mg2+-water results, the newly developed parameters show a better description of the structure and kinetics of the Mg2+-phosphate binding than all other models. The characterization of the ion binding to the riboswitch system shows that the new parameter set does not affect the global structure of the ribonucleic acid system or the number of ions involved in direct or indirect binding. A slight decrease in the number of water-bridged contacts between A-riboswitch and the Mg2+ ion is observed. The results support the ability of the newly developed parameters to improve the kinetic description of the Mg2+ and phosphate ions and their applicability in nucleic acid simulation.