Application of nonlinear dimensionality reduction to characterize the conformational landscape of small peptides.
Application of nonlinear dimensionality reduction to characterize the conformational landscape of small peptides.
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DOI：
10.1002/prot.22526
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发表时间：
2010-02-01
影响因子：
2.9
通讯作者：
Kavraki, Lydia E.
中科院分区：
文献类型：
--
作者：
Stamati, Hernan;Clementi, Cecilia;Kavraki, Lydia E.
关键词：
在计算分子生物物理学中，以几个坐标的形式对模拟中收集的大量分子构型进行自动分类，有助于解释系统的主要状态和跃迁，这是一个反复出现的问题。我们使用最近提出的ScIMAP算法自动提取运动参数的仿真数据。该方法只使用分子形状相似性和拓扑结构信息直接从模拟构象推断，而不是偏见的先验已知信息。自动恢复的坐标被证明是所研究的分子的优良反应坐标，并且可以用于识别稳定状态和过渡，并且作为构建自由能表面的基础。与使用主成分分析（PCA）（最流行的线性降维技术）计算的坐标相比，坐标提供了对自由能景观的更好描述。该方法首先验证了丙氨酸二肽的全原子模型的动力学分析，在那里它成功地恢复所有以前已知的亚稳态。当应用于表征β-发夹的粗粒度模型的模拟折叠时，除了折叠和未折叠状态之外，观察到发夹链的两个对称错误折叠交叉，以及从一个到另一个的最可能的转变。
The automatic classification of the wealth of molecular configurations gathered in simulation in the form of a few coordinates that help explain the main states and transitions of the system is a recurring problem in computational molecular biophysics. We use the recently proposed ScIMAP algorithm to automatically extract motion parameters from simulation data. The procedure uses only molecular shape similarity and topology information inferred directly from the simulated conformations, and is not biased by a priori known information. The automatically-recovered coordinates prove as excellent reaction coordinates for the molecules studied and can be used to identify stable states and transitions, and as a basis to build free-energy surfaces. The coordinates provide a better description of the free energy landscape when compared with coordinates computed using Principal Components Analysis (PCA), the most popular linear dimensionality reduction technique. The method is first validated on the analysis of the dynamics of an all-atom model of alanine dipeptide, where it successfully recover all previously-known metastable states. When applied to characterize the simulated folding of a coarse-grained model of β-hairpin, in addition to the folded and unfolded states, two symmetric misfolding crossings of the hairpin strands are observed, together with the most likely transitions from one to the other.
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影响因子：
4.4
作者：
Christen, M;van Gunsteren, WF
通讯作者：
van Gunsteren, WF
DOI：
10.1073/pnas.100127697
发表时间：
2000-05-23
影响因子：
11.1
作者：
Bolhuis, PG;Dellago, C;Chandler, D
通讯作者：
Chandler, D
影响因子：
1.7
作者：
Chu, J. -W.;Ayton, G. S.;Voth, G. A.
通讯作者：
Voth, G. A.
影响因子：
5.6
作者：
Clementi, C;Nymeyer, H;Onuchic, JN
通讯作者：
Onuchic, JN
影响因子：
3
作者：
Doruker, P;Jernigan, RL;Bahar, I
通讯作者：
Bahar, I