Theoretical and Computational Biophysics Group, NIH Resource Center for Macromolecular Modeling and Visualization, Beckman Institute for Advanced Science and Technology, Department of Biochemistry, Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Int J Mol Sci. 2024 Mar 23;25(7):3616. doi: 10.3390/ijms25073616.
The plasma membrane forms the boundary between a living entity and its environment and acts as a barrier to permeation and flow of substances. Several computational means of calculating permeability have been implemented for molecular dynamics (MD) simulations-based approaches. Except for double bilayer systems, most permeability studies have been performed under equilibrium conditions, in large part due to the challenges associated with creating concentration gradients in simulations utilizing periodic boundary conditions. To enhance the scientific understanding of permeation and complement the existing computational means of characterizing membrane permeability, we developed a non-equilibrium method that enables the generation and maintenance of steady-state gradients in MD simulations. We utilize PBCs advantageously by imposing a directional bias to the motion of permeants so that their crossing of the boundary replenishes the gradient, like a previous study on ions. Under these conditions, a net flow of permeants across membranes may be observed to determine bulk permeability by a direct application of J=PΔc. In the present study, we explore the results of its application to an exemplary O2 and POPC bilayer system, demonstrating accurate and precise permeability measurements. In addition, we illustrate the impact of permeant concentration and the choice of thermostat on the permeability. Moreover, we demonstrate that energetics of permeation can be closely examined by the dissipation of the gradient across the membrane to gain nuanced insights into the thermodynamics of permeability.
细胞膜形成了生命体与其环境之间的边界，并作为物质渗透和流动的屏障。已经有几种计算渗透率的计算方法被应用于基于分子动力学（MD）模拟的方法中。除了双层膜系统外，大多数渗透率研究都是在平衡条件下进行的，这在很大程度上是由于在利用周期性边界条件进行的模拟中创建浓度梯度所带来的挑战。为了增强对渗透的科学理解并补充现有的膜渗透率计算方法，我们开发了一种非平衡方法，该方法能够在 MD 模拟中产生和维持稳态梯度。我们通过对渗透物的运动施加定向偏差来充分利用 PBC 的优势，以便它们穿过边界来补充梯度，就像以前关于离子的研究一样。在这些条件下，可以观察到渗透物穿过膜的净流量，通过直接应用 J=PΔc 来确定总体渗透率。在本研究中，我们探索了将其应用于示例 O2 和 POPC 双层膜系统的结果，证明了准确和精确的渗透率测量。此外，我们说明了渗透物浓度和热库选择对渗透率的影响。此外，我们还证明了可以通过跨膜的梯度耗散来密切检查渗透的能量学，从而深入了解渗透率的热力学。
