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首页> 外文期刊>Computational Biology and Bioinformatics, IEEE/ACM Transactions on >Quantitative Analysis of the Self-Assembly Strategies of Intermediate Filaments from Tetrameric Vimentin
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Quantitative Analysis of the Self-Assembly Strategies of Intermediate Filaments from Tetrameric Vimentin

机译：四聚体波形蛋白中丝的自组装策略的定量分析

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摘要

In vitro assembly of intermediate filaments from tetrameric vimentin consists of a very rapid phase of tetramers laterally associating into unit-length filaments and a slow phase of filament elongation. We focus in this paper on a systematic quantitative investigation of two molecular models for filament assembly, recently proposed in (Kirmse et al. J. Biol. Chem. 282, 52 (2007), 18563-18572), through mathematical modeling, model fitting, and model validation. We analyze the quantitative contribution of each filament elongation strategy: with tetramers, with unit-length filaments, with longer filaments, or combinations thereof. In each case, we discuss the numerical fitting of the model with respect to one set of data, and its separate validation with respect to a second, different set of data. We introduce a high-resolution model for vimentin filament self-assembly, able to capture the detailed dynamics of filaments of arbitrary length. This provides much more predictive power for the model, in comparison to previous models where only the mean length of all filaments in the solution could be analyzed. We show how kinetic observations on low-resolution models can be extrapolated to the high-resolution model and used for lowering its complexity.
机译：四聚体波形蛋白的中间长丝的体外组装包括一个非常快速的四聚体横向结合到单位长度长丝的相和一个缓慢的长丝伸长相。我们在本文中专注于通过数学建模，模型拟合对最近在（Kirmse et al.J.Biol.Chem.282，52（2007），18563-18572）中提出的两种用于长丝组装的分子模型进行系统的定量研究，并进行模型验证。我们分析了每种长丝延伸策略的定量贡献：四聚体，单位长度的长丝，更长的长丝或它们的组合。在每种情况下，我们都会讨论模型相对于一组数据的数值拟合，以及相对于第二组不同数据的模型单独验证。我们介绍了波形蛋白细丝自组装的高分辨率模型，能够捕获任意长度的细丝的详细动态。与仅可以分析溶液中所有细丝的平均长度的以前的模型相比，这为模型提供了更多的预测能力。我们展示了如何将低分辨率模型的动力学观测值外推到高分辨率模型并用于降低其复杂性。

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