The fast-folding hp35 double mutant has a substantially reduced primary folding free energy barrier
文献类型：期刊论文
| 作者 | Lei, Hongxing1,2,3; Deng, Xiaojian1,2; Wang, Zhixiang1,2,4; Duan, Yong1,2 |
| 刊名 | Journal of chemical physics
 |
| 出版日期 | 2008-10-21 |
| 卷号 | 129期号:15页码:7 |
| ISSN号 | 0021-9606 |
| DOI | 10.1063/1.2995987 |
| 通讯作者 | Duan, yong(duan@ucdavis.edu) |
| 英文摘要 | The lys24/29nle double mutant of villin headpiece subdomain (hp35) is the fastest folding protein known so far with a folding time constant of 0.6 mu s. in this work, the folding mechanism of the mutant has been investigated by both conventional and replica exchange molecular dynamics (cmd and remd) simulations with amber ff03 force field and a generalized-born solvation model. direct comparison to the ab initio folding of the wild type hp35 enabled a close examination on the mutational effect on the folding process. the mutant folded to the native state, as demonstrated by the 0.50 a c(alpha)-root mean square deviation (rmsd) sampled in both cmd and remd simulations and the high population of the folded conformation compared with the denatured conformations. consistent with experiments, the significantly reduced primary folding free energy barrier makes the mutant closer to a downhill folder than the wild type hp35 that directly leads to the faster transition and higher melting temperature. however, unlike the proposed downhill folding which envisages a smooth shift between unfolded and folded states without transition barrier, we observed a well-defined folding transition that was consistent with experiments. further examination of the secondary structures revealed that the two mutated residues have higher intrinsic helical preference that facilitated the formation of both helix iii and the intermediate state which contains the folded segment helix ii/iii. other factors contributing to the faster folding include the more favorable electrostatic interactions in the transition state with the removal of the charged nh(3)(+) groups from lys. in addition, both transition state ensemble and denatured state ensemble are shifted in the mutant. (c) 2008 american institute of physics. |
| WOS关键词 | VILLIN HEADPIECE SUBDOMAIN ; MOLECULAR-DYNAMICS SIMULATIONS ; SECONDARY STRUCTURE PROPENSITIES ; EXPERIMENTAL TESTS ; SMALL PROTEINS ; LANDSCAPE ; RESOLUTION ; MUTATIONS ; STABILITY ; PEPTIDES |
| WOS研究方向 | Physics |
| WOS类目 | Physics, Atomic, Molecular & Chemical |
| 语种 | 英语 |
| 出版者 | AMER INST PHYSICS |
| WOS记录号 | WOS:000260280600065 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2391183 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Duan, Yong |
| 作者单位 | 1.Univ Calif Davis, UC Davis Genome Ctr, Davis, CA 95616 USA 2.Univ Calif Davis, Dept Appl Sci, Davis, CA 95616 USA 3.Chinese Acad Sci, Beijing Inst Genom, Beijing 100029, Peoples R China 4.Chinese Acad Sci, Grad Sch, Beijing 100029, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lei, Hongxing,Deng, Xiaojian,Wang, Zhixiang,et al. The fast-folding hp35 double mutant has a substantially reduced primary folding free energy barrier[J]. Journal of chemical physics,2008,129(15):7. |
| APA | Lei, Hongxing,Deng, Xiaojian,Wang, Zhixiang,&Duan, Yong.(2008).The fast-folding hp35 double mutant has a substantially reduced primary folding free energy barrier.Journal of chemical physics,129(15),7. |
| MLA | Lei, Hongxing,et al."The fast-folding hp35 double mutant has a substantially reduced primary folding free energy barrier".Journal of chemical physics 129.15(2008):7. |
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来源：中国科学院大学
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