Water PMF for predicting the properties of water molecules in protein binding site
文献类型：期刊论文
| 作者 | Zheng, Mingyue2 ; Li, Yanlian1; Xiong, Bing1; Jiang, Hualiang2; Shen, Jingkang1
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| 刊名 | JOURNAL OF COMPUTATIONAL CHEMISTRY
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| 出版日期 | 2013-03-15 |
| 卷号 | 34期号:7页码:583-592 |
| 关键词 | potential of mean forces statistical potential scoring function molecular modeling drug design solvent prediction water structure explicit solvent hydration site three-dimensional reference interaction site model |
| ISSN号 | 0192-8651 |
| DOI | 10.1002/jcc.23170 |
| 文献子类 | Article |
| 英文摘要 | 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. (c) 2012 Wiley Periodicals, Inc. |
| WOS关键词 | SELECTIVE ION-BINDING ; LIGAND INTERACTIONS ; SCORING FUNCTIONS ; LIQUID WATER ; INTEGRAL-EQUATION ; MODELING WATER ; HIV-1 PROTEASE ; 3D-RISM THEORY ; DRUG DESIGN ; MEAN FORCE |
| 资助项目 | State Key Laboratory of Drug Research[00000000] ; State Key Program of Basic Research of China[2009CB918502] ; Excellent Young Scientist program of Chinese Academy of Sciences[00000000] ; National Natural Science Foundation of China[81001399] ; National Natural Science Foundation of China[81072580] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000314922800007 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277695]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物发现与设计中心 |
| 通讯作者 | Zheng, Mingyue |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zheng, Mingyue,Li, Yanlian,Xiong, Bing,et al. Water PMF for predicting the properties of water molecules in protein binding site[J]. JOURNAL OF COMPUTATIONAL CHEMISTRY,2013,34(7):583-592. |
| APA | Zheng, Mingyue,Li, Yanlian,Xiong, Bing,Jiang, Hualiang,&Shen, Jingkang.(2013).Water PMF for predicting the properties of water molecules in protein binding site.JOURNAL OF COMPUTATIONAL CHEMISTRY,34(7),583-592. |
| MLA | Zheng, Mingyue,et al."Water PMF for predicting the properties of water molecules in protein binding site".JOURNAL OF COMPUTATIONAL CHEMISTRY 34.7(2013):583-592. |
入库方式： OAI收割
来源：上海药物研究所
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