从增强采样分子动力学模拟中洞察皮肤油氧化产物的真皮渗透。

IF 2.9 2区 化学 Q3 CHEMISTRY, PHYSICAL
The Journal of Physical Chemistry B Pub Date : 2025-02-13 Epub Date: 2025-02-03 DOI:10.1021/acs.jpcb.4c08090
Rinto Thomas, Praveen Ranganath Prabhakar, Douglas J Tobias, Michael von Domaros
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引用次数: 0

摘要

覆盖我们皮肤的脂质混合物皮脂的氧化会产生一系列挥发性和半挥发性羰基化合物,这些化合物在很大程度上导致了拥挤环境中的室内空气污染。动力学模型的发展是为了更深入地了解这种复杂的多相化学,但它们部分依赖于动力学和热力学参数的粗略估计,特别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。我们发现这些模拟是不平凡的,需要广泛的采样,高达微秒的模拟时间,尽管采用增强的采样技术。我们认为膜结构中的高度有序和随机、长时间的不对称性是导致自由能计算缓慢收敛的主要原因。我们证明,由于采样不足造成的统计误差是实质性的,并传播到膜的透性。这些误差与所采用的增强采样技术无关,也很可能与精确的膜模型无关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Insights into Dermal Permeation of Skin Oil Oxidation Products from Enhanced Sampling Molecular Dynamics Simulation.

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.

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来源期刊
CiteScore
5.80
自引率
9.10%
发文量
965
审稿时长
1.6 months
期刊介绍: An essential criterion for acceptance of research articles in the journal is that they provide new physical insight. Please refer to the New Physical Insights virtual issue on what constitutes new physical insight. Manuscripts that are essentially reporting data or applications of data are, in general, not suitable for publication in JPC B.
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