Evolutionary information for specifying a protein fold
Evolutionary information for specifying a protein fold
复制标题
DOI：
10.1038/nature03991
复制
发表时间：
2005-09-22
期刊：
影响因子：
64.8
通讯作者：
Ranganathan, R
中科院分区：
文献类型：
--
作者：
Socolich, M;Lockless, SW;Ranganathan, R
经典研究表明，对于许多蛋白质，指定三级结构所需的信息包含在氨基酸序列中。在这里，我们试图定义的序列规则，用于指定一个蛋白质折叠计算创建人工蛋白质序列，只使用在一个多序列比对编码的统计信息，没有三级结构信息。人工WW结构域序列库的实验测试表明，捕获氨基酸残基之间协同进化的简单统计能量函数对于指定折叠成天然结构的序列是必要且足够的。人工蛋白质表现出类似于天然WW域的热力学稳定性，并且一种人工蛋白质的结构测定在原子分辨率下与WW折叠显示出极好的一致性。用于创建序列的信息的相对简单性表明蛋白质折叠问题的潜在复杂性显著降低。
Classical studies show that for many proteins, the information required for specifying the tertiary structure is contained in the amino acid sequence. Here, we attempt to define the sequence rules for specifying a protein fold by computationally creating artificial protein sequences using only statistical information encoded in a multiple sequence alignment and no tertiary structure information. Experimental testing of libraries of artificial WW domain sequences shows that a simple statistical energy function capturing coevolution between amino acid residues is necessary and sufficient to specify sequences that fold into native structures. The artificial proteins show thermodynamic stabilities similar to natural WW domains, and structure determination of one artificial protein shows excellent agreement with the WW fold at atomic resolution. The relative simplicity of the information used for creating sequences suggests a marked reduction to the potential complexity of the protein- folding problem.