Phylogeny of protein-folding trajectories reveals a unique pathway to native structure
Phylogeny of protein-folding trajectories reveals a unique pathway to native structure
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DOI：
10.1073/pnas.0407015102
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发表时间：
2004-12-21
影响因子：
11.1
通讯作者：
Kidera, A
中科院分区：
文献类型：
--
作者：
Ota, M;Ikeguchi, M;Kidera, A
为了仔细研究蛋白质如何以原子分辨率折叠，我们在计算网格上对微型蛋白色氨酸笼进行了 200 次分子动力学模拟（每次 50 纳秒）。在这些轨迹中，识别出了 58 个折叠事件和 31 个展开事件，并进行了广泛的比较和分类。基于与生物序列的类比，折叠和展开轨迹（结构的连续快照阵列）通过允许间隙的动态编程来对齐。从比对得出的系统发育树揭示了四组不同的轨迹，其特征是色氨酸侧链运动和主链运动。结果发现，只有一组获得了天然结构，其他三组产生了具有正确主链轨迹但具有不同非天然色氨酸侧链旋转异构体的假结构，表明这四种折叠结构都是通过独特的折叠途径获得的。
To scrutinize how a protein folds at atomic resolution, we performed 200 molecular dynamics simulations (each of 50 ns) of the miniprotein Trp-cage on the computational grid. Within the trajectories, 58 folding and 31 unfolding events were identified and subjected to extensive comparison and classification. Based on an analogy with biological sequences, the folding and unfolding trajectories (arrays of sequential snapshots of structures) were aligned by dynamic programming allowing gaps. A phylogenetic tree derived from the alignments revealed four distinct groups of the trajectories, characterized by the Trp side-chain motions and the main-chain motions. It was found that only one group attained the native structure and that the other three led to pseudonative structures having the correct main-chain trace but different nonnative Trp side-chain rotamers, indicating that those four folded structures were each attained through a unique folding pathway.