模拟可电离分子的皮肤透过程
Magnus Lundborg1,2, Christian Wennberg1,3, Erik Lindahl4,5
1SciLifeLab, ERCO Pharma AB, 171 65 Solna, Sweden.
Journal of chemical information and modeling
|June 25, 2024
概括
可电离药物分子穿透皮肤屏障. 虽然动态质子化模拟提供了洞察力,但皮肤透系数的计算只能依赖这些分子的中性形式.
科学领域:
- 药理动力学 药理动力学
- 计算化学计算化学
- 材料科学 材料科学 材料科学
背景情况:
- 电离性分子,如药物,在制药中至关重要.
- 皮肤屏障对药物输送具有重大挑战.
- 目前的模型通常假定中性药物物种的被动扩散.
研究的目的:
- 为了研究皮肤透过程中可电离分子的动态质子化行为.
- 确定是否需要动态质突模拟来计算皮肤透系数.
- 为了比较弱酸与弱通过脂质双层的透.
主要方法:
- 使用了分子动力学 (MD) 模拟.
- 对分子的充电状态和中性状态进行了单独的模拟.
- 在脂质屏障模型中研究了三个弱酸和三个弱.
主要成果:
- 弱酸在pKa附近的脂质头组区域显示出比弱更高的电离.
- 动态质子化模拟提供了关于分子行为的信息数据.
- 然而,这些动态模拟在研究的案例中对于透系数计算来说并不必不可少.
结论:
- 皮肤透性计算只能有效地利用电离分子中性形式.
- 假设中性形式的透性足以计算透系数.
- 了解动态质子是有价值的,但并不总是需要进行定量预测.
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