Water PMF for predicting the properties of water molecules in protein binding site
Water PMF for predicting the properties of water molecules in protein binding site
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水 PMF 用于预测蛋白质结合位点中水分子的特性
DOI：
10.1002/jcc.23170
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发表时间：
2013-03
影响因子：
3
通讯作者：
J. Shen
中科院分区：
文献类型：
--
作者：
M. Zheng;Y. Li;B. Xiong;H. Jiang;J. Shen
水是生命系统中的重要组成部分，应该在化学和生物学上得到更好的理解。然而，由于研究蛋白质结构中水功能的难度较大，在计算建模中，特别是在计算机辅助药物设计领域，它往往被忽视。在这里，我们使用平均力势(PMF)方法，构造了基于3946个非冗余高分辨晶体结构的水PMF(WPMF)。首次利用提取的WPMF势研究了水的结构模式，分析了水的残留物亲水性。然后，研究了结晶水的WPMF评分与B因子之间的关系。结果表明，WPMF与以前报道的一些实验观测结果符合得很好。此外，WPMF评分还与3D-RISM并行测试，以衡量提取实验观测水域的能力，并显示出类似的性能，但计算量要小得多。最后，我们提出了一种基于网格的聚类方法，并结合距离加权的WPMF评分，进一步扩展了WPMF来预测蛋白质结构的潜在水合位置。经测试，该方法在计算得分低于−4.0时，预测水化部位的准确率可达80%左右。它还允许在配基设计中评估给定的水分子是否应该作为置换的目标。总体而言，这里介绍的WPMF为许多与水相关的计算建模问题提供了一个可选的解决方案，其中一些作为合理药物设计策略的一部分可能具有很高的价值。©2012 Wiley期刊，Inc.
Water is an important component in living systems and deserves better understanding in chemistry and biology. However, due to the difficulty of investigating the water functions in protein structures, it is usually ignored in computational modeling, especially in the field of computer‐aided drug design. Here, using the potential of mean forces (PMFs) approach, we constructed a water PMF (wPMF) based on 3946 non‐redundant high resolution crystal structures. The extracted wPMF potential was first used to investigate the structure pattern of water and analyze the residue hydrophilicity. Then, the relationship between wPMF score and the B factor value of crystal waters was studied. It was found that wPMF agrees well with some previously reported experimental observations. In addition, the wPMF score was also tested in parallel with 3D‐RISM to measure the ability of retrieving experimentally observed waters, and showed comparable performance but with much less computational cost. In the end, we proposed a grid‐based clustering scheme together with a distance weighted wPMF score to further extend wPMF to predict the potential hydration sites of protein structure. From the test, this approach can predict the hydration site at the accuracy about 80% when the calculated score lower than −4.0. It also allows the assessment of whether or not a given water molecule should be targeted for displacement in ligand design. Overall, the wPMF presented here provides an optional solution to many water related computational modeling problems, some of which can be highly valuable as part of a rational drug design strategy. © 2012 Wiley Periodicals, Inc.
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DOI：
10.1098/rstb.2004.1495
发表时间：
2004-08-29
影响因子：
6.3
作者：
Finney, JL
通讯作者：
Finney, JL
影响因子：
15
作者：
Abel, Robert;Young, Tom;Friesner, Richard A.
通讯作者：
Friesner, Richard A.
影响因子：
15
作者：
N. Yoshida;S. Phongphanphanee;Y. Maruyama;T. Imai;F. Hirata
通讯作者：
N. Yoshida;S. Phongphanphanee;Y. Maruyama;T. Imai;F. Hirata
影响因子：
15
作者：
Imai, Takashi;Oda, Koji;Kidera, Akinori
通讯作者：
Kidera, Akinori
影响因子：
7.3
作者：
Amadasi, Alessio;Surface, J. Andrew;Kellogg, Glen E.
通讯作者：
Kellogg, Glen E.