Protein Folding Pathways Extracted by OFLOOD: Outlier FLOODing Method
Protein Folding Pathways Extracted by OFLOOD: Outlier FLOODing Method
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DOI：
10.1002/jcc.23773
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发表时间：
2015-01-15
影响因子：
3
通讯作者：
Shigeta, Yasuteru
中科院分区：
文献类型：
--
作者：
Harada, Ryuhei;Nakamura, Tomotake;Shigeta, Yasuteru
离群FLOODing方法（OFLOOD）被提出作为一种有效的构象采样方法，以提取生物罕见的事件，如蛋白质折叠。在OFLOOD中，稀疏分布（构象空间中的离群值）被视为转换的相关状态。然后，通过从异常值的构象恢复增强转变。这一证据表明，稀疏分布的构象恢复可能会增加促进从异常值到其他亚稳态的转变的机会，这类似于从异常值到相邻簇的构象洪水。OFLOOD包括（i）从构象分布中检测离群值和（ii）通过分子动力学（MD）模拟从离群值中检测构象。（i）和（ii）的循环简单地重复。作为示范，OFLOOD应用于Chignolin和HP 35的折叠。在这两种情况下，OFLOOD自动提取折叠路径展开的结构与ns阶计算成本，虽然μ s阶规范MD未能提取它们。(c)2014 Wiley Periodicals，Inc.
The Outlier FLOODing method (OFLOOD) is proposed as an efficient conformational sampling method to extract biologically rare events such as protein folding. In OFLOOD, sparse distributions (outliers in the conformational space) were regarded as relevant states for the transitions. Then, the transitions were enhanced through conformational resampling from the outliers. This evidence indicates that the conformational resampling of the sparse distributions might increase chances for promoting the transitions from the outliers to other meta-stable states, which resembles a conformational flooding from the outliers to the neighboring clusters. OFLOOD consists of (i) detections of outliers from conformational distributions and (ii) conformational resampling from the outliers by molecular dynamics (MD) simulations. Cycles of (i) and (ii) are simply repeated. As demonstrations, OFLOOD was applied to folding of Chignolin and HP35. In both cases, OFLOOD automatically extracted folding pathways from unfolded structures with ns-order computational costs, although mu s-order canonical MD failed to extract them. (c) 2014 Wiley Periodicals, Inc.