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Mapping Central alpha-Helix Linker Mediated Conformational Transition Pathway of Calmodulin via Simple Computational Approach

文献类型：期刊论文

作者Wang, Jinan1; Peng, Shaoliang3,4; Cossins, Benjamin P.2; Liao, Xiangke3,4; Chen, Kaixian1; Shao, Qiang1; Zhu, Xiaoqian3,4; Shi, Jiye2; Zhu, Weiliang1
刊名JOURNAL OF PHYSICAL CHEMISTRY B
出版日期2014-08-14
卷号118期号:32页码:9677-9685
ISSN号1520-6106
DOI10.1021/jp507186h
文献子类Article
英文摘要The effects of intrinsic structural flexibility of calmodulin protein on the mechanism of its allosteric conformational transition are investigated in this article. Using a novel in silico approach, the conformational transition pathways of intact calmodulin as well as the isolated N- and C-terminal domains are identified and energetically characterized. It is observed that the central alpha-helix linker amplifies the structural flexibility of intact Ca2+-free calmodulin, which might facilitate the transition of the two domains. As a result, the global conformational transition of Ca2+-free calmodulin is initiated by the barrierless transition of two domains and proceeds through the barrier associated unwinding and bending of the central alpha-helix linker. The binding of Ca2+ cations to calmodulin further increases the structural flexibility of the C-terminal domain and results in a downhill transition pathway of which all regions transit in a concerted manner. On the other hand, the separation of the N- and C-terminal domains from calmodulin protein loses the mediating function of central alpha-helix linker, leading to more difficult conformational transitions of both domains. The present study provides novel insights into the correlation of the integrity of protein, the structural flexibility, and the mechanism of conformational transition of proteinlike calmodulin.
WOS关键词NORMAL-MODE ANALYSIS ; HISTOGRAM ANALYSIS METHOD ; FREE-ENERGY CALCULATIONS ; MOLECULAR-DYNAMICS ; INTRINSIC DYNAMICS ; CALCIUM AFFINITY ; SHIFT MECHANISM ; FORCE-FIELD ; DOMAIN ; SIMULATIONS
资助项目National 863 Program[2012AA01A305] ; National Natural Science Foundation of China (NNSFC)[21373258] ; National Natural Science Foundation of China (NNSFC)[21021063] ; National Basic Research Program of China (973)[2014CB910400] ; National Basic Research Program of China (973)[2012CB910400]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000340443100015
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/276946]  
专题药物发现与设计中心
通讯作者Shao, Qiang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China;
2.UCB Pharma, Slough SL1 4EN, Berks, England
3.Natl Univ Def Technol, State Key Lab High Performance Comp, Changsha 410073, Hunan, Peoples R China;
4.Natl Univ Def Technol, Sch Comp Sci, Changsha 410073, Hunan, Peoples R China;
推荐引用方式
GB/T 7714		 Wang, Jinan,Peng, Shaoliang,Cossins, Benjamin P.,et al. Mapping Central alpha-Helix Linker Mediated Conformational Transition Pathway of Calmodulin via Simple Computational Approach[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2014,118(32):9677-9685.
APA Wang, Jinan.,Peng, Shaoliang.,Cossins, Benjamin P..,Liao, Xiangke.,Chen, Kaixian.,...&Zhu, Weiliang.(2014).Mapping Central alpha-Helix Linker Mediated Conformational Transition Pathway of Calmodulin via Simple Computational Approach.JOURNAL OF PHYSICAL CHEMISTRY B,118(32),9677-9685.
MLA Wang, Jinan,et al."Mapping Central alpha-Helix Linker Mediated Conformational Transition Pathway of Calmodulin via Simple Computational Approach".JOURNAL OF PHYSICAL CHEMISTRY B 118.32(2014):9677-9685.

入库方式： OAI收割

来源：上海药物研究所

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