二氧化硫分子通过增强二次成核促进纤维的生长:基于分子动力学的模拟研究

Sulfur Dioxide Promotes the Formation of Amyloid Fibrils through Enhanced Secondary Nucleation: A Molecular Dynamics Study

空气污染是一种常见的现象.空气污染物是诱发各类疾病的重要因素之一.以二氧化硫分子为代表,研究了它与Aβ17-42原纤维之间的相互作用.伞形抽样模拟表明,二氧化硫分子的引入减少了纤维的解离自由能.分析各氨基酸残基结合二氧化硫的频数得知,二氧化硫分子更容易动态地结合到疏水性氨基酸残基的骨架上,同时也容易结合到带电的氨基酸残基上进而削弱盐桥相互作用,但是对这些相互作用的削弱是非常微小的,不足以破坏原纤维的结构.通过非线性主方程分析,我们发现二氧化硫分子加速了Aβ17-42二次成核过程,同时缩短了迟滞时间而加速纤维的聚集过程.通过这些计算,我们定量地揭示了空气污染物与蛋白质相互作用的特征,期望我们的结果为当今社会评估污染物的健康效应提供宝贵的参考信息.

Air pollution is a common phenomenon in developing countries, and pollutants are suggested to be essential reasons to produce various diseases, such as cancers, neuro-degenerative diseases and so on. In present work, the effects of sulfur dioxide on the dissociation of Aβ17-42 peptides from core region of Aβ fibril were studied with umbrella sampling method. It is found that the free energy penalty related to the dissociation processes would decrease for larger concentrations of sulfur dioxide. The detailed interactions between peptides and sulfur dioxide are analyzed based on contact statistics. It is suggested that the destabilization of the Aβ fibril is realized by the binding of sulfur dioxide with the peptide backbone as well as the side chains of charged residues, which results in the decrease of hydrophobic interaction and blockage of the electrostatic interactions between charged residues. Furthermore, the positive contribution of such a marginal destabilization on the growth of fibril is also discussed with a nonlinear master equation, which is consistent with the medical knowledge. Through these computations, we disclose the characteristics of the interactions between air pollutants and protein molecules. We expect that these results could help to assess the effect of air pollutants on human health.