Solvent Structure and Dynamics near the Surfaces of β-Hematin Crystals
Solvent Structure and Dynamics near the Surfaces of β-Hematin Crystals
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DOI：
10.1021/acs.jpcb.1c06589
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发表时间：
2021-10-05
影响因子：
3.3
通讯作者：
Palmer，Jeremy C.
中科院分区：
文献类型：
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作者：
Verma，Laksmanji;Vekilov，Peter G.;Palmer，Jeremy C.
血红素结晶是疟原虫生理学的重要组成部分，也是抗疟药物最成功的靶点，在体内和体外的混合有机-水溶剂中进行。在这里，我们采用分子动力学模拟研究的结构和动力学的水-正辛醇混合物（溶剂，模仿的环境主办血红素crystalizationin体内）在附近的典型面的习性的血红素晶体。模拟结果表明，溶剂在邻近晶体的层中的性质受到每个晶面所呈现的不同化学和拓扑特征的强烈影响。溶剂组织成至少三个不同的层。我们还表明，结构附近的不同面的β-高铁血红素的溶剂强烈影响的界面动力学。正辛醇分子的弛豫时间在接触层中最长，并且与在相应面处的结构有序度相关。我们表明，宏观上均匀的水-辛醇溶液中含有水和正辛醇的氢键，截留了大部分的水，但大多小于30个水分子连接的集群。靠近晶体表面的簇锚在血红素羧基。这些结果提供了一个直接的例子，溶剂结构化不限于水和其他氢键的解决方案。我们的研究结果阐明了血红素结晶机制的两个基本特征：天然和合成血红素晶体的细长形状和通过包裹在水簇中来稳定血红素和抗疟药的带电基团。此外，这些研究结果表明，血红素结晶可以控制添加剂，破坏或加强溶剂结构。
Hematin crystallization, which is an essential component of the physiology of malaria parasites and the most successful target for antimalarial drugs, proceeds in mixed organic–aqueous solvents bothin vivoandin vitro. Here we employ molecular dynamics simulations to examine the structuring and dynamics of a water–normal octanol mixture (a solvent that mimics the environment hosting hematin crystallizationin vivo) in the vicinity of the typical faces in the habit of a hematin crystal. The simulations reveal that the properties of the solvent in the layer adjacent to the crystal are strongly impacted by the distinct chemical and topological features presented by each crystal face. The solvent organizes into at least three distinct layers. We also show that structuring of the solvent near the different faces of β-hematin strongly impacts the interfacial dynamics. The relaxation time ofn-octanol molecules is longest in the contact layers and correlates with the degree of structural ordering at the respective face. We show that the macroscopically homogeneous water–octanol solution holds clusters of water andn-octanol connected by hydrogen bonds that entrap the majority of the water but are mostly smaller than 30 water molecules. Near the crystal surface the clusters anchor on hematin carboxyl groups. These results provide a direct example that solvent structuring is not restricted to aqueous and other hydrogen-bonded solutions. Our findings illuminate two fundamental features of the mechanisms of hematin crystallization: the elongated shapes of natural and synthetic hematin crystals and the stabilization of charged groups of hematin and antimalarials by encasing in water clusters. In addition, these findings suggest that hematin crystallization may be controlled by additives that disrupt or reinforce solvent structuring.