Learning about Biomolecular Solvation from Water in Protein Crystals
Learning about Biomolecular Solvation from Water in Protein Crystals
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DOI：
10.1021/acs.jpcb.7b09898
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发表时间：
2018-03-08
影响因子：
3.3
通讯作者：
Charbonneau, Patrick
中科院分区：
文献类型：
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作者：
Altan, Irem;Fusco, Diana;Charbonneau, Patrick
水通常占蛋白质晶体的50%，因此在晶体学实验中对衍射信号有显着贡献。然而，将其贡献与蛋白质的贡献分开是具有挑战性的，因为大多数水分子不是局部的，因此难以分配到特定的密度峰。蛋白质-水界面的复杂性加剧了这一困难。因此，这些信息并不常用于研究生物分子的溶剂化。在这里，我们开发了一种方法来克服部分这一困难。更具体地说，我们比较了从衍射数据获得的溶剂结构，实验相位可从约束分子动力学（MD）模拟。由此产生的空间密度图表明，常用的MD水模型是唯一部分成功地再现生物分子溶剂化的结构特征。水的径向分布仅以比其角分布略高的精度被捕获，并且仅恢复了以高可靠性分配给晶体结构的一小部分水分子。这些差异可能是由于水模型和蛋白质力场的缺点。尽管有这些限制，我们设法推断质子化状态的一些侧链利用MD衍生的密度。
Water occupies typically 50% of a protein crystal and thus significantly contributes to the diffraction signal in crystallography experiments. Separating its contribution from that of the protein is, however, challenging because most water molecules are not localized and are thus difficult to assign to specific density peaks. The intricateness of the protein-water interface compounds this difficulty. This information has, therefore, not often been used to study biomolecular solvation. Here, we develop a methodology to surmount in part this difficulty. More specifically, we compare the solvent structure obtained from diffraction data for which experimental phasing is available to that obtained from constrained molecular dynamics (MD) simulations. The resulting spatial density maps show that commonly used MD water models are only partially successful at reproducing structural features of biomolecular solvation. The radial distribution of water is captured with only slightly higher accuracy than its angular distribution, and only a fraction of the water molecules assigned with high reliability to the crystal structure is recovered. These differences are likely due to shortcomings of both the water models and the protein force fields. Despite these limitations, we manage to infer protonation states of some of the side chains utilizing MD-derived densities.