This article presents atomistic molecular dynamics and umbrella sampling simulations of levodopa at various concentrations in hydrated cholesterol-free 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. Levodopa is the standard medication for Parkinson's disease and is marketed under various trade names; in the context of this article, the levodopa molecule is mostly studied in its zwitterionic form but some results concerning the neutral levodopa are presented as well for comparison purposes. The motivation is to study in detail how levodopa behaves in different hydrated lipid membranes, primarily from the thermodynamic point of view, and reveal aspects of mechanism of its permeation through them. Dependencies of properties on the levodopa concentration are also investigated. Special attention is paid to the calculation of mass density profiles, order parameters and self-diffusion coefficients. Levodopa zwitterions, which form a hydrogen bond network with water and phospholipid molecules, are found to be preferentially located at the water/lipid interface, as well as in the aqueous phase surrounding the cholesterol-free and cholesterol-containing bilayers. This is concluded from the potentials of mean force calculated by umbrella sampling simulations as levodopa is transferred from the lipid to the aqueous phase along an axis perpendicular to the two leaflets of the membranes.

本文介绍了左旋多巴在不同浓度的水合无胆固醇 1,2-二棕榈酰-sn-甘油-3-磷酸胆碱 (DPPC) 和含胆固醇的 1-棕榈酰-2-油酰-sn- 中的原子分子动力学和伞状采样模拟甘油-3-磷酸胆碱 (POPC) 双层。左旋多巴是帕金森病的标准药物，以各种商品名销售；在本文中，左旋多巴分子主要以其两性离子形式进行研究，但也提供了一些关于中性左旋多巴的结果以供比较。其动机是主要从热力学的角度详细研究左旋多巴在不同水合脂质膜中的行为，并揭示其渗透机制的各个方面。还研究了性质对左旋多巴浓度的依赖性。特别注意质量密度分布、顺序参数和自扩散系数的计算。发现与水和磷脂分子形成氢键网络的左旋多巴两性离子优先位于水/脂质界面以及围绕无胆固醇和含胆固醇双层的水相中。这是从通过伞形采样模拟计算的平均力的电位得出的结论，因为左旋多巴沿着垂直于膜的两个小叶的轴从脂质转移到水相。发现它们与水和磷脂分子形成氢键网络，优先位于水/脂质界面，以及围绕无胆固醇和含胆固醇双层的水相中。这是从通过伞形采样模拟计算的平均力的电位得出的结论，因为左旋多巴沿着垂直于膜的两个小叶的轴从脂质转移到水相。发现它们与水和磷脂分子形成氢键网络，优先位于水/脂质界面，以及围绕无胆固醇和含胆固醇双层的水相中。这是从通过伞形采样模拟计算的平均力的电位得出的结论，因为左旋多巴沿着垂直于膜的两个小叶的轴从脂质转移到水相。