Water PMF for predicting the properties of water molecules in protein binding site

doi:10.1002/jcc.23170

	Water PMF for predicting the properties of water molecules in protein binding site
	Zheng, Mingyue2 ; Li, Yanlian 1; Xiong, Bing1 ; Jiang, Hualiang2 ; Shen, Jingkang 1
刊名	JOURNAL OF COMPUTATIONAL CHEMISTRY
	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.
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
WOS研究方向	Chemistry
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000314922800007
内容类型	期刊论文
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.