Clustering of low-energy conformations near the native structures of small proteins
Clustering of low-energy conformations near the native structures of small proteins
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DOI：
10.1073/pnas.95.19.11158
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发表时间：
1998-09-15
影响因子：
11.1
通讯作者：
Baker, D
中科院分区：
文献类型：
--
作者：
Shortle, D;Simons, KT;Baker, D
最近的实验研究的变性状态和理论分析的折叠景观表明，有一个大的多样性的低能量，部分折叠构象附近的原生状态。在这份报告中，我们描述了一种基于工作假设的预测蛋白质结构的策略，即正确折叠周围的低能构象比周围的低能不正确折叠更多，为了测试这个想法，12个500比1的集合，通过计算系综中每个构象和每个其他构象之间的Car坐标的均方根偏差，分析了10个小蛋白质的000个低能结构。在所有12种情况下，具有4埃rms偏差内的最大数量的构象的构象比系综中的大多数构象更接近天然结构，并且在大多数情况下，它是最接近的1至5%。这些结果表明，有效地折叠和保持稳健性的氨基酸序列的变化，蛋白质可能已经进化出一个天然的结构，位于一个广泛的盆地内的低能量构象，一个功能，可以促进蛋白质结构的预测在低分辨率。
Recent experimental studies of the denatured state and theoretical analyses of the folding landscape suggest that there are a large multiplicity of low-energy, partially folded conformations near the native state. In this report, we describe a strategy for predicting protein structure based on the working hypothesis that there are a greater number of low-energy conformations surrounding the correct fold than there are surrounding low-energy incorrect folds, To test this idea, 12 ensembles of 500 to 1,000 low-energy structures for 10 small proteins were analyzed by calculating the rms deviation of the Car coordinates between each conformation and every other conformation in the ensemble. In all 12 cases, the conformation with the greatest number of conformations within 4-Angstrom rms deviation was closer to the native structure than were the majority of conformations in the ensemble, and in most cases it was among the closest I to 5%. These results suggest that, to fold efficiently and retain robustness to changes in amino acid sequence, proteins may have evolved a native structure situated within a broad basin of low-energy conformations, a feature which could facilitate the prediction of protein structure at low resolution.