Native protein sequences are close to optimal for their structures
Native protein sequences are close to optimal for their structures
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DOI：
10.1073/pnas.97.19.10383
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发表时间：
2000-09-12
影响因子：
11.1
通讯作者：
Baker, D
中科院分区：
文献类型：
--
作者：
Kuhlman, B;Baker, D
与给定蛋白质结构兼容的序列空间量有多大？从随机序列开始，通过使用蒙特卡罗优化程序以及主要基于伦纳德 - 琼斯堆积相互作用和拉扎里迪斯 - 卡普拉斯隐式溶剂化模型的自由能函数，为108个蛋白质主链结构生成了低自由能序列。值得注意的是，在设计的序列中，51%的核心残基和27%的所有残基与天然序列中相应位置的氨基酸相同。为类天然主链结构集合获得的最低自由能序列也与天然序列相似。此外，在非常大的SH3结构域家族中观察到的单个残基频率以及位置对之间的协方差，在为SH3结构域结构设计的核心序列中得以重现。综上所述，这些结果表明，对蛋白质结构而言最佳的序列空间量令人惊讶地局限于天然序列周围的区域。
How large is the volume of sequence space that is compatible with a given protein structure? starting from random sequences, low free energy sequences were generated for 108 protein backbone structures by using a Monte Carlo optimization procedure and a free energy function based primarily on Lennard-Jones packing interactions and the Lazaridis-Karplus implicit solvation model. Remarkably, in the designed sequences 51% of the core residues and 27% of all residues were identical to the amino acids in the corresponding positions in the native sequences. The lowest free energy sequences obtained for ensembles of native-like backbone structures were also similar to the native sequence. Furthermore. both the individual residue frequencies and the covariances between pairs of positions observed in the very large SH3 domain family were recapitulated in core sequences designed for SH3 domain structures. Taken together, these results suggest that the volume of sequence space optimal for a protein structure is surprisingly restricted to a region around the native sequence.