Quantifying Induced Dipole Effects in Small Molecule Permeation in a Model Phospholipid Bilayer,The Journal of Physical Chemistry B

当前位置： X-MOL 学术 › J. Phys. Chem. B › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Quantifying Induced Dipole Effects in Small Molecule Permeation in a Model Phospholipid Bilayer
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2024-07-22 , DOI: 10.1021/acs.jpcb.4c01634
Julia M Montgomery ₁ , Justin A Lemkul _{1,

2}

Affiliation

The cell membrane functions as a semipermeable barrier that governs the transport of materials into and out of cells. The bilayer features a distinct dielectric gradient due to the amphiphilic nature of its lipid components. This gradient influences various aspects of small molecule permeation and the folding and functioning of membrane proteins. Here, we employ polarizable molecular dynamics simulations to elucidate the impact of the electronic environment on the permeation process. We simulated eight distinct amino-acid side chain analogs within a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer using the Drude polarizable force field (FF). Our approach includes both unbiased and umbrella sampling simulations. By using a polarizable FF, we sought to investigate explicit dipole responses in relation to local electric fields along the membrane normal. We evaluate molecular dipole moments, which exhibit variation based on their localization within the membrane, and compare the outcomes with analogous simulations using the nonpolarizable CHARMM36 FF. This comparative analysis aims to discern characteristic differences in the free energy surfaces of permeation for the various amino-acid analogs. Our results provide the first systematic quantification of the impact of employing an explicitly polarizable FF in this context compared to the fixed-charge convention inherent to nonpolarizable FFs, which may not fully capture the influence of the membrane dielectric gradient.

中文翻译：

量化磷脂双层模型中小分子渗透的诱导偶极效应

细胞膜充当半透屏障，控制物质进出细胞的运输。由于其脂质成分的两亲性质，双层具有明显的介电梯度。这种梯度影响小分子渗透以及膜蛋白的折叠和功能的各个方面。在这里，我们采用可极化分子动力学模拟来阐明电子环境对渗透过程的影响。我们使用 Drude 极化力场 (FF) 模拟了 1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱双层内的八种不同的氨基酸侧链类似物。我们的方法包括无偏抽样模拟和伞式抽样模拟。通过使用可极化 FF，我们试图研究与沿膜法线的局部电场相关的显式偶极子响应。我们评估分子偶极矩（分子偶极矩根据其在膜内的定位而表现出变化），并将结果与使用非极化 CHARMM36 FF 的类似模拟进行比较。该比较分析旨在辨别各种氨基酸类似物渗透自由能表面的特征差异。与非极化 FF 固有的固定电荷惯例相比，我们的结果首次系统地量化了在这种情况下使用明确可极化 FF 的影响，这可能无法完全捕获膜介电梯度的影响。

更新日期：2024-07-22

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文