Mechanism of pyrophosphate ion release in T7 RNA polymerase revealed by free energy simulations

doi:http://dx.doi.org/10.1016/j.comptc.2016.09.005

ITP OpenIR > SCI期刊论文

	Wu, SG; Jiang, MQ; Liu, L; Wu, SG (reprint author), Sichuan Normal Univ, Coll Chem & Mat Sci, Chengdu 610068, Peoples R China.
	Mechanism of pyrophosphate ion release in T7 RNA polymerase revealed by free energy simulations
发表期刊	COMPUTATIONAL AND THEORETICAL CHEMISTRY (IF:1.443[JCR-2017],1.404[5-Year])
语种	英语
关键词	Molecular Dynamics Simulation T7 Rna Polymerase Ppi Release Potential Of Mean Force
摘要	In this article, we explored pyrophosphate ion (PPi) release mechanism in T7 RNAP using all-atom free energy simulations in explicit solvent. Steered Molecular Dynamics (SMD) and Umbrella Sampling (US) methods were combined to estimate the potential of mean force (PMF) for the PPi release in T7 RNAP. PPi is a small group with negative charges. After binding a Mg2+ ion, the formed (Mg-PPi)(2-) complex is able to bind with both positively and negatively charged groups. Our simulation results show there is a large free energy barrier in the PMF profile for PPi release. Non-bonded interaction analysis suggests that the PPi is firmly trapped in the pore region of the secondary channel, which is composed of many polar, negatively and positively charged groups. Strong electric interactions from the surrounding groups contribute mostly to the high energy barrier for PPi release. Hydrogen bond map clearly exhibits part of the interaction network that the PPi has been trapped in. Therefore, we conclude that PPi is less likely to be released spontaneously. Additional energy input is needed to facilitate this process. It is deduced that NTP addition reaction may serve as an energy provider to drive PPi release. Then the whole NAC mechanism can be well explained. It is expected that our study provides a clear picture on the essential step of RNA transcription at atom-level resolution. (C) 2016 Elsevier B.V. All rights reserved.
	2016
卷号	1094 页码:127-132
学科领域	Chemistry
DOI	http://dx.doi.org/10.1016/j.comptc.2016.09.005
收录类别	SCI
项目资助者	National Natural Science Foundation of China [11405113] ; National Natural Science Foundation of China [11405113] ; National Natural Science Foundation of China [11405113] ; National Natural Science Foundation of China [11405113] ; Science and Technology Plan of Sichuan Province, China [2010JY0122] ; Science and Technology Plan of Sichuan Province, China [2010JY0122] ; Science and Technology Plan of Sichuan Province, China [2010JY0122] ; Science and Technology Plan of Sichuan Province, China [2010JY0122]
引用统计	正在获取...
文献类型	期刊论文
条目标识符	http://ir.itp.ac.cn/handle/311006/21505
专题	SCI期刊论文
通讯作者	Wu, SG (reprint author), Sichuan Normal Univ, Coll Chem & Mat Sci, Chengdu 610068, Peoples R China.
推荐引用方式 GB/T 7714	Wu, SG,Jiang, MQ,Liu, L,et al. Mechanism of pyrophosphate ion release in T7 RNA polymerase revealed by free energy simulations[J]. COMPUTATIONAL AND THEORETICAL CHEMISTRY,2016,1094:127-132.
APA	Wu, SG,Jiang, MQ,Liu, L,&Wu, SG .(2016).Mechanism of pyrophosphate ion release in T7 RNA polymerase revealed by free energy simulations.COMPUTATIONAL AND THEORETICAL CHEMISTRY,1094,127-132.
MLA	Wu, SG,et al."Mechanism of pyrophosphate ion release in T7 RNA polymerase revealed by free energy simulations".COMPUTATIONAL AND THEORETICAL CHEMISTRY 1094(2016):127-132.

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