Karolinska Institutet, Department of Biosciences and Nutrition, Center for Biosciences, SE-141 83 HUDDINGE, Sweden.
J Chem Theory Comput. 2012 Apr 10;8(4):1493-502. doi: 10.1021/ct3000734. Epub 2012 Mar 22.
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 Mg(2+) ions and also for the biologically relevant ions Na(+), K(+), and Ca(2+) together with three different water models (TIP3P, SPC/E, and TIP5P). The results show that Mg(2+) ions have a slower exchange rate than Na(+), K(+), and Ca(2+) in agreement with the experimental trend, but the simulated value underestimates the experimentally observed Mg(2+)-water exchange rate by several orders of magnitude, irrespective of the force field and water model. A new set of parameters for Mg(2+) 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 Mg(2+) binding with a monophosphate model system and with the purine riboswitch, add A-riboswitch. In line with the Mg(2+)-water results, the newly developed parameters show a better description of the structure and kinetics of the Mg(2+)-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 Mg(2+) ion is observed. The results support the ability of the newly developed parameters to improve the kinetic description of the Mg(2+) and phosphate ions and their applicability in nucleic acid simulation.
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。为了正确模拟这些生物物理过程，应用的分子模型应该能够再现离子在水溶液中的动力学性质。在这里，我们使用分子动力学模拟详细研究了镁离子与水分子和核酸系统结合的动力学。我们验证了生物分子力场（如 AMBER 和 CHARMM）中用于镁离子的参数，以及与三种不同水模型（TIP3P、SPC/E 和 TIP5P）一起的生物相关离子 Na(+)、K(+)和 Ca(2+)的参数。结果表明，Mg(2+)离子的交换速率比 Na(+)、K(+)和 Ca(2+)慢，这与实验趋势一致，但模拟值低估了实验观察到的 Mg(2+)-水交换速率，相差几个数量级，无论力场和水模型如何。开发了一组新的镁离子参数来重现实验动力学数据。该参数集还可以比现有模型更好地重现结构数据。我们将新参数集应用于单磷酸模型系统和嘌呤核糖开关 add A-riboswitch 与镁离子的结合。与 Mg(2+)-水的结果一致，新开发的参数集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。对离子与核糖开关系统结合的表征表明，新参数集不会影响核糖核酸系统的整体结构或直接或间接结合的离子数量。观察到 A-riboswitch 与镁离子之间的水桥接接触数量略有减少。结果支持新开发参数集改善镁离子和磷酸盐离子动力学描述的能力及其在核酸模拟中的适用性。
