...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Folding free energy function selects native-like protein sequences in the core but not on the surface
【24h】

Folding free energy function selects native-like protein sequences in the core but not on the surface

机译：折叠自由能功能在核心而不是表面选择天然蛋白序列

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

An automatic protein design procedure is used to select amino acid sequences that optimize the folding free energy function for a given protein. The only information used in designing the sequences is a set of known backbone structures for each protein, a rotamer library, and a well established classical empirical force field, which relies on basic physical chemical principles that underlie molecular interactions and protein stability, and has not been adjusted to yield native-like sequences. Applying the procedure to 7 different known protein folds, representing a total of 45 different native protein structures, yields ensembles of designed sequences displaying remarkable similarity to their natural counterparts in the protein core, but which are distinctly non-native on the protein surface. We show that natural and designed sequences for a given fold score significantly higher than random sequences against profiles derived from both, designed and natural sequence ensembles. Furthermore, we find that designed sequence profiles can be used to retrieve the native sequences for many of the analyzed proteins using standard PSI-BLAST searches in sequence databases. These findings may have important implications for our understanding the selection pressures operating on natural protein sequences and hold promise for improving fold recognition.
机译：自动蛋白质设计程序用于选择氨基酸序列，以优化给定蛋白质的折叠自由能功能。设计序列时使用的唯一信息是每种蛋白质的一组已知主链结构，旋转异构体文库和一个完善的经典经验力场，该场依靠分子相互作用和蛋白质稳定性基础的基本物理化学原理，并且没有被调整以产生类似天然的序列。将程序应用于7种不同的已知蛋白质折叠（代表总共45种不同的天然蛋白质结构），可产生设计序列的集合，这些序列与蛋白质核心中的天然对应物显示出显着的相似性，但在蛋白质表面上显然是非天然的。我们表明，针对给定倍数的自然序列和设计序列比针对源自既有设计序列又有自然序列集合的配置文件的随机序列要高得多。此外，我们发现设计的序列图谱可用于在序列数据库中使用标准PSI-BLAST搜索来检索许多分析蛋白质的天然序列。这些发现可能对我们理解天然蛋白质序列上的选择压力具有重要意义，并有望改善折叠识别。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号