Biomolecular Solvation Structure Revealed by Molecular Dynamics Simulations.
Biomolecular Solvation Structure Revealed by Molecular Dynamics Simulations.
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分子动力学模拟揭示的生物分子溶剂化结构。
DOI：
10.1021/jacs.8b13613
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发表时间：
2019
影响因子：
15
通讯作者：
Warren,GregoryL
中科院分区：
文献类型：
--
作者：
Wall,MichaelE;Calabró,Gaetano;Bayly,ChristopherI;Mobley,DavidL;Warren,GregoryL
为了比较有序水的位置从实验与那些从分子动力学（MD）模拟，在结晶内切葡聚糖酶的水结构的MD模型的数量进行了计算。起始MD模型来自于联合X射线和中子衍射晶体结构，使得能够使用实验指定的质子化状态。在结晶状态下，使用具有明确溶剂的周期性2 × 2 × 2超原胞进行模拟。水的X射线和中子散射密度图计算从MD轨迹使用标准的大分子晶体学方法。在一组模拟中，应用谐波约束来使蛋白质结构偏向晶体结构。对于这些模拟，使用MD水电子密度中的强峰的结晶沃茨的回忆是非常好的，并且中子散射密度和结晶水氢位置的回旋镖状翅膀之间也有实质性的视觉一致性。还进行了无约束模拟。对于这种模拟，晶体沃茨的召回率要低得多。对于约束和无约束的模拟，最强的水密度峰值与结晶沃茨。结果表明，它现在是可能的，以恢复结晶水结构，使用限制MD模拟，但它还没有合理的期望无限制MD模拟做同样的。进一步的发展和推广的MD水模型力场的发展，大分子晶体学，和药物化学的应用，现在是必要的。特别是，室温晶体学，中子衍射和结晶MD模拟相结合，有望大大推进生物分子溶剂化的建模。
To compare ordered water positions from experiment with those from molecular dynamics (MD) simulations, a number of MD models of water structure in crystalline endoglucanase were calculated. The starting MD model was derived from a joint X-ray and neutron diffraction crystal structure, enabling the use of experimentally assigned protonation states. Simulations were performed in the crystalline state, using a periodic 2 × 2 × 2 supercell with explicit solvent. Water X-ray and neutron scattering density maps were computed from MD trajectories using standard macromolecular crystallography methods. In one set of simulations, harmonic restraints were applied to bias the protein structure toward the crystal structure. For these simulations, the recall of crystallographic waters using strong peaks in the MD water electron density was very good, and there also was substantial visual agreement between the boomerang-like wings of the neutron scattering density and the crystalline water hydrogen positions. An unrestrained simulation also was performed. For this simulation, the recall of crystallographic waters was much lower. For both restrained and unrestrained simulations, the strongest water density peaks were associated with crystallographic waters. The results demonstrate that it is now possible to recover crystallographic water structure using restrained MD simulations but that it is not yet reasonable to expect unrestrained MD simulations to do the same. Further development and generalization of MD water models for force-field development, macromolecular crystallography, and medicinal chemistry applications is now warranted. In particular, the combination of room-temperature crystallography, neutron diffraction, and crystalline MD simulations promises to substantially advance modeling of biomolecular solvation.