Universidad Rey Juan Carlos, ESCET, Mostoles, 28933 Madrid, Spain.
Department of Chemistry, The University of Utah, Salt Lake City, Utah 84112-0850, USA.
J Chem Phys. 2021 Oct 21;155(15):154502. doi: 10.1063/5.0063986.
Water diffusion through membrane proteins is a key aspect of cellular function. Essential processes of cellular metabolism are driven by osmotic pressure, which depends on water channels. Membrane proteins such as aquaporins (AQPs) are responsible for enabling water permeation through the cell membrane. AQPs are highly selective, allowing only water and relatively small polar molecules to cross the membrane. Experimentally, estimation of water flux through membrane proteins is still a challenge, and hence, accurate simulations of water permeation are of particular importance. We present a numerical study of water diffusion through AQP1 comparing three water models: TIP3P, OPC, and TIP4P/2005. Bulk diffusion, diffusion permeability, and osmotic permeability are computed and compared among all models. The results show that there are significant differences between TIP3P (a particularly widespread model for simulations of biological systems) and the more recently developed TIP4P/2005 and OPC models. We demonstrate that OPC and TIP4P/2005 reproduce protein-water interactions and dynamics in very good agreement with experimental data. From this study, we find that the choice of the water model has a significant effect on the computed water dynamics as well as its molecular behavior within a biological nanopore.
水通过膜蛋白的扩散是细胞功能的一个关键方面。细胞代谢的基本过程是由渗透压驱动的,而渗透压又取决于水通道。水通道蛋白(AQP)等膜蛋白负责使水通过细胞膜渗透。AQP 具有高度选择性,只允许水和相对较小的极性分子通过膜。在实验中,通过膜蛋白的水通量的估计仍然是一个挑战,因此,水渗透的准确模拟尤其重要。我们通过比较三种水分子模型(TIP3P、OPC 和 TIP4P/2005)对 AQP1 中的水扩散进行了数值研究。我们计算并比较了所有模型的体相扩散、扩散渗透率和渗透渗透率。结果表明,TIP3P(一种特别广泛用于模拟生物系统的模型)与最近开发的 TIP4P/2005 和 OPC 模型之间存在显著差异。我们证明了 OPC 和 TIP4P/2005 能够很好地再现蛋白质-水相互作用和动力学,与实验数据非常吻合。通过这项研究,我们发现水分子模型的选择对计算水动力学以及其在生物纳米孔内的分子行为有显著影响。