A parameter estimation technique for stochastic self-assembly systems and its application to human papillomavirus self-assembly.
A parameter estimation technique for stochastic self-assembly systems and its application to human papillomavirus self-assembly.
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DOI：
10.1088/1478-3975/7/4/045005
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发表时间：
2010-12-09
期刊：
影响因子：
2
通讯作者：
Schwartz R
中科院分区：
文献类型：
--
作者：
Kumar MS;Schwartz R
病毒衣壳组装一直是复杂自组装研究的关键模型系统，但对建模研究也提出了一些重大挑战。一个重要的限制是很难确定准确的速率参数。典型病毒的大小和快速组装使得直接测量外壳蛋白结合率或从现有的相对间接的实验方法中推断它们是不可行的。在目前的工作中，我们开发了一种计算策略，通过将随机模拟轨迹与组装过程的实验测量相匹配，来推断病毒衣壳组装系统的外套结合率参数。我们的方法结合了二次响应面和准梯度下降近似来处理模拟的高计算量、模拟轨迹中的随机噪声以及可用实验数据的限制。该方法在人乳头瘤病毒(HPV)体外组装系统的光散射轨迹上进行了验证，表明该方法可以推断出准确的曲线拟合的速率参数，并且与先前的数据分析具有很好的一致性。这些拟合提供了对体外系统潜在组装机制的洞察，并为探索这些机制在体外和体内组装条件下的变化提供了基础。
Virus capsid assembly has been a key model system for studies of complex self-assembly but does pose some significant challenges for modeling studies. One important limitation is the difficulty of determining accurate rate parameters. The large size and rapid assembly of typical viruses make it infeasible to directly measure coat protein binding rates or infer them from the relatively indirect experimental measures available. In the present work, we develop a computational strategy to infer coat-coat binding rate parameters for viral capsid assembly systems by fitting stochastic simulation trajectories to experimental measures of assembly progress. Our method combines quadratic response surface and quasi-gradient-descent approximations to deal with the high computational cost of simulations, stochastic noise in simulation trajectories, and limitations of the available experimental data. The approach is demonstrated on a light scattering trajectory for a human papillomavirus (HPV) in vitro assembly system, showing that the method can infer rate parameters that produce accurate curve fits and are in good concordance with prior analysis of the data. These fits provide insight into potential assembly mechanisms of the in vitro system and a basis for exploring how these mechanisms might vary between in vitro and in vivo assembly conditions.
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影响因子：
2.9
作者：
Ceres, P;Zlotnick, A
通讯作者：
Zlotnick, A
影响因子：
3.4
作者：
CASPAR, DLD
通讯作者：
CASPAR, DLD
影响因子：
3.4
作者：
PREVELIGE, PE;THOMAS, D;KING, J
通讯作者：
KING, J
DOI：
10.1073/pnas.91.16.7732
发表时间：
1994-08-02
影响因子：
11.1
作者：
BERGER, B;SHOR, PW;KING, J
通讯作者：
KING, J
影响因子：
2.7
作者：
Johnston, Iain G.;Louis, Ard A.;Doye, Jonathan P. K.
通讯作者：
Doye, Jonathan P. K.