Rational Design of Particle Mesh Ewald Compatible Lennard-Jones Parameters for +2 Metal Cations in Explicit Solvent.
Rational Design of Particle Mesh Ewald Compatible Lennard-Jones Parameters for +2 Metal Cations in Explicit Solvent.
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DOI：
10.1021/ct400146w
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发表时间：
2013-06-11
影响因子：
5.5
通讯作者：
Merz, Kenneth M., Jr.
中科院分区：
文献类型：
--
作者：
Li, Pengfei;Roberts, Benjamin P.;Chakravorty, Dhruva K.;Merz, Kenneth M., Jr.
金属离子在生物系统中起着重要的作用。对这些系统进行精确的分子动力学（MD）模拟需要一组经过验证的参数。虽然有更详细的方法来模拟金属离子，非键模型，它采用了12-6 Lennard-Jones（LJ）项加上静电势仍然广泛用于今天的MD模拟由于其简单的形式。但由于组合规则不同、水模型多样、模拟方法多样，LJ参数的可移植性有限。最近，采用粒子网格埃瓦尔德（PME）处理远程静电的模拟由于其速度和精度而变得越来越流行。在目前的工作中，我们系统地设计了24 + 2金属（M（II））阳离子的LJ参数，以重现不同的实验性质，适合于Lorentz-Berthelot结合规则和PME模拟。我们开始测试目前可用的M（II）离子LJ参数的可转移性。结果表明，采用埃瓦尔德求和与其他模拟方法的模拟之间存在差异，并且有必要设计新的参数，具体用于基于PME的模拟。采用热力学积分（TI）方法和执行周期性边界MD模拟采用PME，允许系统的调查LJ参数空间。对四种常用水模型（TIP 3 P、SPC/E、TIP 4P和TIP 4PEW）的LJ势参数进行了不同组合，得到了水化自由能（HFEs）、第一溶剂化壳层离子-氧距离（IOD）和配位数（CN）。结果表明，这三个模拟的性质是高度相关的。同时，具有相同参数的M（II）离子在不同的水模型中产生显着不同的HFE，但相似的结构特性。由于非键模型低估了金属离子与水分子之间的短程相互作用，因此很难同时重现各种实验值。TIP 3 P、SPC/E、TIP 4PEW和TIP 4P水模型的低估程度依次增大。尽管如此，我们还是拟合了一条曲线来描述ε（阱深）和半径（Rmin/2）之间的关系，这些关系来自惰性气体的实验数据，以便于生成最佳的折衷模型。因此，通过针对不同的实验值，我们为三种不同的水模型（TIP 3 P、SPC/E和TIP 4PEW）开发了三组M（II）阳离子参数。我们认为这些参数代表了使用非键合离子模型结合简单水模型可以实现的最佳折衷。根据计算不确定性分析，我们估计计算的HFE的不确定性约为± 1 kcal/mol。进一步的改进将需要更先进的非粘结模型，可能包括极化。
Metal ions play significant roles in biological systems. Accurate molecular dynamics (MD) simulations on these systems require a validated set of parameters. Although there are more detailed ways to model metal ions, the nonbonded model, which employs a 12-6 Lennard-Jones (LJ) term plus an electrostatic potential is still widely used in MD simulations today due to its simple form. However, LJ parameters have limited transferability due to different combining rules, various water models and diverse simulation methods. Recently, simulations employing a Particle Mesh Ewald (PME) treatment for long-range electrostatics have become more and more popular owing to their speed and accuracy. In the present work we have systematically designed LJ parameters for 24 +2 metal (M(II)) cations to reproduce different experimental properties appropriate for the Lorentz-Berthelot combining rules and PME simulations. We began by testing the transferability of currently available M(II) ion LJ parameters. The results showed that there are differences between simulations employing Ewald summation with other simulation methods and that it was necessary to design new parameters specific for PME based simulations. Employing the thermodynamic integration (TI) method and performing periodic boundary MD simulations employing PME, allowed for the systematic investigation of the LJ parameter space. Hydration free energies (HFEs), the ion-oxygen distance in the first solvation shell (IOD) and coordination numbers (CNs) were obtained for various combinations of the parameters of the LJ potential for four widely used water models (TIP3P, SPC/E, TIP4P and TIP4PEW). Results showed that the three simulated properties were highly correlated. Meanwhile, M(II) ions with the same parameters in different water models produce remarkably different HFEs but similar structural properties. It is difficult to reproduce various experimental values simultaneously because the nonbonded model underestimates the interaction between the metal ions and water molecules at short range. Moreover, the extent of underestimation increases successively for the TIP3P, SPC/E, TIP4PEW and TIP4P water models. Nonetheless, we fitted a curve to describe the relationship between ε (the well depth) and radius (Rmin/2) from experimental data on noble gases to facilitate the generation of the best possible compromise models. Hence, by targeting different experimental values, we developed three sets of parameters for M(II) cations for three different water models (TIP3P, SPC/E and TIP4PEW). These parameters we feel represent the best possible compromise that can be achieved using the nonbonded model for the ions in combination with simple water models. From a computational uncertainty analysis we estimate that the uncertainty in our computed HFEs is on the order of ±1kcal/mol. Further improvements will require more advanced non-bonded models likely with inclusion of polarization.
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