Thomas Rinto, Prabhakar Praveen Ranganath, Tobias Douglas J, von Domaros Michael
Fachbereich Chemie, Philipps-Universität Marburg, Marburg 35032, Germany.
Department of Chemistry, University of California, Irvine, Irvine, California 92697, United States.
J Phys Chem B. 2025 Feb 13;129(6):1784-1794. doi: 10.1021/acs.jpcb.4c08090. Epub 2025 Feb 3.
The oxidation of human sebum, a lipid mixture covering our skin, generates a range of volatile and semivolatile 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 nontrivial, 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.
人类皮脂是覆盖在我们皮肤上的一种脂质混合物，其氧化会产生一系列挥发性和半挥发性羰基化合物，这些化合物在很大程度上导致了拥挤环境中的室内空气污染。人们已经开发了动力学模型来更深入地理解这种复杂的多相化学过程，但这些模型部分依赖于对动力学和热力学参数的粗略估计，尤其是那些描述皮肤渗透的参数。在这里，我们采用原子分子动力学模拟来研究选定的皮肤油脂氧化产物通过模型角质层膜的转运。我们发现这些模拟并非易事，尽管采用了增强采样技术，但仍需要长达微秒的模拟时间进行广泛采样。我们确定膜结构中高度的有序性和随机的、长期存在的时间不对称性是自由能计算收敛缓慢的主要原因。我们证明，由于采样不足导致的统计误差很大，并会传播到膜渗透率上。这些误差与所采用的增强采样技术无关，而且很可能与精确的膜模型无关。
