基于增强采样分子动力学模拟的皮肤油脂氧化产物经皮渗透洞察
Insights into Dermal Permeation of Skin Oil Oxidation Products from Enhanced Sampling Molecular Dynamics Simulation
AI总结：
本研究利用原子级分子动力学与增强采样模拟皮肤油脂氧化产物穿过角质层膜的过程，揭示微秒级充分采样的必要性及膜结构导致自由能收敛缓慢的机制。
摘要：
人体皮脂（覆盖在我们皮肤表面的一种脂质混合物）的氧化会产生一系列挥发性和半挥发性羰基化合物，这些化合物在拥挤环境中对室内空气污染有很大贡献。为了更深入地理解这一复杂的多相化学过程，研究人员已经建立了动力学模型，但这些模型在一定程度上依赖于对动力学和热力学参数的粗略估计，尤其是描述皮肤渗透的参数。在此，我们采用原子级分子动力学模拟，研究选定的皮肤油脂氧化产物通过模型角质层膜的转位过程。我们发现这些模拟并非易事：尽管使用了增强采样技术，仍需进行高达微秒级模拟时间的大量采样。我们将膜结构的高度有序性以及随机、长寿命的时间不对称性确定为自由能计算收敛缓慢的主要原因。我们证明，采样不足导致的统计误差相当大，并会传播到膜渗透率中。这些误差与所采用的增强采样技术无关，并且很可能与具体的膜模型无关。
英文摘要：
The oxidation of human sebum, a lipid mixture covering our skin, generates a range of volatile and semi-volatile carbonyl compounds that contribute largely to indoor air pollution in crowded environments. Kinetic models have been developed to gain a deeper understanding of this complex multiphase chemistry, but they rely partially on rough estimates of kinetic and thermodynamic parameters, especially those describing skin permeation. Here, we employ atomistic molecular dynamics simulations to study the translocation of selected skin oil oxidation products through a model stratum corneum membrane. We find these simulations to be non-trivial, requiring extensive sampling with up to microsecond simulation times, in spite of employing enhanced sampling techniques. We identify the high degree of order and stochastic, long-lived temporal asymmetries in the membrane structure as the leading causes for the slow convergence of the free energy computations. We demonstrate that statistical errors due to insufficient sampling are substantial and propagate to membrane permeabilities. These errors are independent of the enhanced sampling technique employed and very likely independent of the precise membrane model.
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