Probing the protein corona around charged macromolecules: interpretation of isothermal titration calorimetry by binding models and computer simulations
Probing the protein corona around charged macromolecules: interpretation of isothermal titration calorimetry by binding models and computer simulations
复制标题
探测带电大分子周围的蛋白质电晕：通过结合模型和计算机模拟解释等温滴定量热法
DOI：
10.1007/s00396-020-04648-x
复制
发表时间：
2020-04
影响因子：
2.4
通讯作者：
Dzubiella Joachim
中科院分区：
文献类型：
--
作者：
Xu Xiao;Dzubiella Joachim
等温滴定量热法（ITC）是一种广泛使用的工具，用于实验探测大分子或纳米颗粒周围蛋白质冠形成的热信号。如果将适当的结合模型应用于ITC数据，则可以定量和解释结合热和结合化学计量以及每个蛋白质的结合亲和力。然而，蛋白质与大分子的结合受到复杂的微观相互作用的控制。特别地，由于冠内的空间和静电蛋白质-蛋白质相互作用以及总复合物的协同电荷重整化效应，标准（例如，Langmuir）结合模型是有问题的，并且开发更合适的结合模型是非常具有挑战性的。在这里，我们讨论了最近的事态发展，在解释的Langmuir模型应用到ITC的数据的蛋白质电晕形成，举例说明了定义明确的情况下，溶菌酶涂层高度带电的树枝状聚甘油硫酸酯（dPGS），并表明，有意义的数据可以提取的拟合，如果适当的分析。正如我们所展示的，这对于通过分子计算机模拟来解释ITC数据特别有用，其中可以计算结合亲和力，但通常不清楚如何将它们与ITC数据进行一致的比较。此外，我们讨论了连接的Langmuir模型连续结合模型（其中没有离散的结合位点必须假设）及其可能的扩展对包括领先的顺序合作静电效应。
Isothermal titration calorimetry (ITC) is a widely used tool to experimentally probe the heat signal of the formation of the protein corona around macromolecules or nanoparticles. If an appropriate binding model is applied to the ITC data, the heat of binding and the binding stoichiometry as well as the binding affinity per protein can be quantified and interpreted. However, the binding of the protein to the macromolecule is governed by complex microscopic interactions. In particular, due to the steric and electrostatic protein-protein interactions within the corona as well as cooperative, charge renormalization effects of the total complex, the application of standard (e.g., Langmuir) binding models is questionable and the development of more appropriate binding models is very challenging. Here, we discuss recent developments in the interpretation of the Langmuir model applied to ITC data of protein corona formation, exemplified for the well-defined case of lysozyme coating highly charged dendritic polyglycerol sulfate (dPGS), and demonstrate that meaningful data can be extracted from the fits if properly analyzed. As we show, this is particular useful for the interpretation of ITC data by molecular computer simulations where binding affinities can be calculated but it is often not clear how to consistently compare them with the ITC data. Moreover, we discuss the connection of Langmuir models to continuum binding models (where no discrete binding sites have to be assumed) and their possible extensions toward the inclusion of leading order cooperative electrostatic effects.
登录
查看更多内容
DOI：
10.1063/1.4958675
发表时间：
2016-02
期刊：
The Journal of chemical physics
影响因子：
--
作者：
Xiao Xu;M. Kanduč;Jianzhong Wu;J. Dzubiella
通讯作者：
Xiao Xu;M. Kanduč;Jianzhong Wu;J. Dzubiella
影响因子：
64.8
作者：
M. Muir
通讯作者：
M. Muir
DOI：
10.1021/acs.jpcb.9b07448
发表时间：
2019-09
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Xiao Xu;M. Ballauff
通讯作者：
Xiao Xu;M. Ballauff
影响因子：
16.6
作者：
Lo Giudice, Maria Cristina;Herda, Luciana M.;Polo, Ester;Dawson, Kenneth A.
通讯作者：
Dawson, Kenneth A.
DOI：
10.1039/b609879g
发表时间：
2006-11
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
A. Wittemann;Matthias Ballauff
通讯作者：
A. Wittemann;Matthias Ballauff