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Molecular dynamics simulations of β2-microglobulin interaction with hydrophobic surfaces
Molecular BioSystems Pub Date : 2017-10-09 00:00:00 , DOI: 10.1039/c7mb00464h
Cedrix J. Dongmo Foumthuim 1, 2, 3, 4 , Alessandra Corazza 1, 2, 3, 4, 5 , Gennaro Esposito 4, 5, 6, 7, 8 , Federico Fogolari 2, 3, 4, 7, 8
Affiliation  

Hydrophobic surfaces are known to adsorb and unfold proteins, a process that has been studied only for a few proteins. Here we address the interaction of β2-microglobulin, a paradigmatic protein for the study of amyloidogenesis, with hydrophobic surfaces. A system with 27 copies of the protein surrounded by a model cubic hydrophobic box is studied by implicit solvent molecular dynamics simulations. Most proteins adsorb on the walls of the box without major distortions in local geometry, whereas free molecules maintain proper structures and fluctuations as observed in explicit solvent molecular dynamics simulations. The major conclusions from the simulations are as follows: (i) the adopted implicit solvent model is adequate to describe protein dynamics and thermodynamics; (ii) adsorption occurs readily and is irreversible on the simulated timescale; (iii) the regions most involved in molecular encounters and stable interactions with the walls are the same as those that are important in protein–protein and protein–nanoparticle interactions; (iv) unfolding following adsorption occurs at regions found to be flexible by both experiments and simulations; (v) thermodynamic analysis suggests a very large contribution from van der Waals interactions, whereas unfavorable electrostatic interactions are not found to contribute much to adsorption energy. Surfaces with different degrees of hydrophobicity may occur in vivo. Our simulations show that adsorption is a fast and irreversible process which is accompanied by partial unfolding. The results and the thermodynamic analysis presented here are consistent with and rationalize previous experimental work.

中文翻译:

β2-微球蛋白与疏水表面相互作用的分子动力学模拟

疏水性表面可吸附和展开蛋白质,这是仅针对少数几种蛋白质进行研究的过程。在这里,我们讨论β2-微球蛋白(一种用于研究淀粉样蛋白生成的范例蛋白)与疏水表面的相互作用。通过隐式溶剂分子动力学模拟研究了具有27个蛋白质副本的模型立方疏水盒包围的系统。大多数蛋白质吸附在盒子的壁上,局部几何结构没有重大变形,而自由分子则保持适当的结构和波动,如在显式溶剂分子动力学模拟中观察到的那样。从模拟得出的主要结论如下:(i)所采用的隐式溶剂模型足以描述蛋白质动力学和热力学;(ii)吸附很容易发生,并且在模拟的时间尺度上是不可逆的;(iii)与分子接触和与壁的稳定相互作用最相关的区域与那些在蛋白质-蛋白质和蛋白质-纳米粒子相互作用中重要的区域相同;(iv)通过实验和模拟发现,吸附后的展开发生在柔软的区域;(v)热力学分析表明范德华相互作用的贡献很大,而不利的静电相互作用对吸附能的贡献却不大。可能会出现疏水程度不同的表面 (iv)通过实验和模拟发现,吸附后的展开发生在柔软的区域;(v)热力学分析表明范德华相互作用的贡献很大,而不利的静电相互作用对吸附能的贡献却不大。可能会出现疏水程度不同的表面 (iv)通过实验和模拟发现,吸附后的展开发生在柔软的区域;(v)热力学分析表明范德华相互作用的贡献很大,而不利的静电相互作用对吸附能的贡献却不大。可能会出现疏水程度不同的表面体内。我们的模拟表明吸附是一个快速且不可逆的过程,并伴随着部分展开。此处给出的结果和热力学分析与先前的实验工作一致并合理化。
更新日期:2017-10-21
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