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DOI | 10.1038/s41467-019-11161-5 |
Large enhancement of response times of a protein conformational switch by computational design | |
DeGrave, Alex J.1; Ha, Jeung-Hoi2; Loh, Stewart N.2; Chong, Lillian T.1 | |
2019-07-30 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | The design of protein conformational switches-or proteins that change conformations in response to a signal such as ligand binding-has great potential for developing novel biosensors, diagnostic tools, and therapeutic agents. Among the defining properties of such switches, the response time has been the most challenging to optimize. Here we apply a computational design strategy in synergistic combination with biophysical experiments to rationally improve the response time of an engineered protein-based Ca2+-sensor in which the switching process occurs via mutually exclusive folding of two alternate frames. Notably, our strategy identifies mutations that increase switching rates by as much as 32-fold, achieving response times on the order of fast physiological Ca2+ fluctuations. Our computational design strategy is general and may aid in optimizing the kinetics of other protein conformational switches. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000427027200001 |
WOS关键词 | ENSEMBLE BROWNIAN DYNAMICS ; WEIGHTED-ENSEMBLE ; MOLECULAR SIMULATIONS ; FLUORESCENT PROTEINS ; CALCIUM-BINDING ; ASSOCIATION ; TRANSITION ; MECHANISM ; EFFICIENT ; STATE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204470 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA; 2.SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA |
推荐引用方式 GB/T 7714 | DeGrave, Alex J.,Ha, Jeung-Hoi,Loh, Stewart N.,et al. Large enhancement of response times of a protein conformational switch by computational design[J]. NATURE COMMUNICATIONS,2019,9. |
APA | DeGrave, Alex J.,Ha, Jeung-Hoi,Loh, Stewart N.,&Chong, Lillian T..(2019).Large enhancement of response times of a protein conformational switch by computational design.NATURE COMMUNICATIONS,9. |
MLA | DeGrave, Alex J.,et al."Large enhancement of response times of a protein conformational switch by computational design".NATURE COMMUNICATIONS 9(2019). |
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