Locating missing water molecules in protein cavities by the three-dimensional reference interaction site model theory of molecular solvation
Locating missing water molecules in protein cavities by the three-dimensional reference interaction site model theory of molecular solvation
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DOI：
10.1002/prot.21311
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发表时间：
2007-03-01
影响因子：
2.9
通讯作者：
Hirata, Fumio
中科院分区：
文献类型：
--
作者：
Imai, Takashi;Hiraoka, Ryusuke;Hirata, Fumio
蛋白质空腔中的水分子对于理解蛋白质的结构和功能具有重要意义。然而，通过普通的分子模拟和模拟技术以及实验方法来定位蛋白质中的水分子是一个不平凡的任务。本研究证明，三维参考相互作用位点模型（3D-RISM）理论，最近发展的分子溶剂化的物理力学理论，在定位这样的水分子有突出的优势。在本文中，我们证明了3D-RISM理论是能够再现的结构和水分子的数量在鸡蛋白溶菌酶腔中观察到的常见的X射线结构的不同分辨率和条件。此外，我们表明，该理论成功地确定了一个水分子在一个空腔，其存在一直是模糊的，即使从X射线的结果。与此相反，我们证实，分子动力学模拟是无助的，目前找到这样的水分子，因为结果基本上取决于水分子的初始坐标。该理论在生物化学和生物物理学领域的问题可能的应用也进行了讨论。
Water molecules confined in protein cavities are of great importance in understanding the protein structure and functions. However, it is a nontrivial task to locate such water molecules in protein by the ordinary molecular simulation and modeling techniques as well as experimental methods. The present study proves that the three-dimensional reference interaction site model (3D-RISM) theory, a recently developed statistical-mechanical theory of molecular solvation, has an outstanding advantage in locating such water molecules. In this paper, we demonstrate that the 3D-RISM theory is able to reproduce the structure and the number of water molecules in cavities of hen egg-white lysozyme observed commonly in the Xray structures of different resolutions and conditions. Furthermore, we show that the theory successfully identified a water molecule in a cavity, the existence of which has been ambiguous even from the X-ray results. In contrast, we confirmed that molecular dynamics simulation is helpless at present to find such water molecules because the results substantially depend on the initial coordinates of water molecules. Possible applications of the theory to problems in the fields of biochemistry and biophysics are also discussed.