On the origin and highly likely completeness of single-domain protein structures
On the origin and highly likely completeness of single-domain protein structures
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DOI：
10.1073/pnas.0509379103
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发表时间：
2006-02-21
影响因子：
11.1
通讯作者：
Skolnick, J
中科院分区：
文献类型：
--
作者：
Zhang, Y;Hubner, IA;Skolnick, J
蛋白质折叠宇宙的大小和起源具有根本和实际意义。分析在通用简化和全原子蛋白质模型中构建的随机生成的紧凑的粘性同源多肽构象，在已求解结构的库即蛋白质数据库中都具有相似的折叠，相反，蛋白质数据库中的所有紧凑的单域蛋白质结构在紧凑模型集中都具有结构类似物。因此，这两组蛋白质很可能是完整的，蛋白质折叠宇宙是由氢键二级结构的紧密构象产生的。由于侧链由其C-β原子表示，这些结果也表明观察到的蛋白质折叠对侧链堆积的细节不敏感。序列特异性既可以微调结构，也可以相对于一组备选方案在热力学上稳定给定的折叠。对照三维活动网站库扫描模型，经常会发现紧密的几何匹配。因此，活性中心类几何结构的存在似乎也是紧凑的二级结构元素堆积的结果。这些结果对蛋白质结构和功能的进化具有重要意义。
The size and origin of the protein fold universe is of fundamental and practical importance. Analyzing randomly generated, compact sticky homopolypeptide conformations constructed in generic simplified and all-atom protein models, all have similar folds in the library of solved structures, the Protein Data Bank, and conversely, all compact, single-domain protein structures in the Protein Data Bank have structural analogues in the compact model set. Thus, both sets are highly likely complete, with the protein fold universe arising from compact conformations of hydrogen-bonded, secondary structures. Because side chains are represented by their C-beta atoms, these results also suggest that the observed protein folds are insensitive to the details of side-chain packing. Sequence specificity enters both in fine-tuning the structure and thermodynamically stabilizing a given fold with respect to the set of alternatives. Scanning the models against a three-dimensional active-site library, close geometric matches are frequently found. Thus, the presence of active-site-like geometries also seems to be a consequence of the packing of compact, secondary structural elements. These results have significant implications for the evolution of protein structure and function.