Computing osmotic permeabilities of aquaporins AQP4, AQP5, and GlpF from near-equilibrium simulations.
Computing osmotic permeabilities of aquaporins AQP4, AQP5, and GlpF from near-equilibrium simulations.
复制标题
通过近平衡模拟计算水通道蛋白 AQP4、AQP5 和 GlpF 的渗透率。
DOI：
10.1016/j.bbamem.2017.04.022
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Chen,LiaoY
中科院分区：
文献类型：
--
作者：
Wambo,ThierryO;Rodriguez,RobertoA;Chen,LiaoY
测量或计算水通道蛋白/水甘油通道蛋白（AQP）的单通道渗透性一直是一个挑战。测量值分散在一个数量级，但相应的阿克里尼乌斯激活能收敛在目前的文献。通过AQP的渗透通量被模拟为通过通道的水流，其通过的压力是通过水的压力或理论上近似为单列扩散。在本文中，我们报告了大规模模拟的渗透流下通过三个AQP（水通道AQP 4和AQP 5和甘油-水通道GlpF）使用成熟的粒子网格埃瓦尔德技术（PME），其中建立的力场已被优化，已知的精度。这些模拟是用混合周期性边界条件实现的，该边界条件旨在避免在常规PME模拟中跨膜的人工产物混合。在5 °C和25 °C下计算的单通道渗透率与最近改进的GlpF实验一致。从我们的模拟中提取的所有三种AQP的Arrhenius活化能与体外测量结果一致。从我们的大规模模拟的单行扩散近似与当前的文献中较小的系统是一致的。从这些明确的协议thein vitroandin silicosstudies之间，我们观察到目前文献的水通道生物学的全原子力场的定量准确性。我们还观察到，在中枢神经系统中特别丰富的AQP 4在水传导中更有效，并且比其他仅水通道（不包括在不被甘油抑制时也传导水的甘油通道）更对温度敏感。
Measuring or computing the single-channel permeability of aquaporins/aquaglyceroporins (AQPs) has long been a challenge. The measured values scatter over an order of magnitude but the corresponding Arrhenius activation energies converge in the current literature. Osmotic flux through an AQP was simulated as water current forced through the channel by kilobar hydraulic pressure or theoretically approximated as single-file diffusion. In this paper, we report large scale simulations of osmotic current under sub M gradient through three AQPs (water channels AQP4 and AQP5 and glycerol-water channel GlpF) using the mature particle mesh Ewald technique (PME) for which the established force fields have been optimized with known accuracy. These simulations were implemented with hybrid periodic boundary conditions devised to avoid the artifactitious mixing across the membrane in a regular PME simulation. The computed single-channel permeabilities at 5 °C and 25 °C are in agreement with recently refined experiments on GlpF. The Arrhenius activation energies extracted from our simulations for all the three AQPs agree with thein vitromeasurements. The single-file diffusion approximations from our large-scale simulations are consistent with the current literature on smaller systems. From these unambiguous agreements among thein vitroandin silicostudies, we observe the quantitative accuracy of the all-atom force fields of the current literature for water-channel biology. We also observe that AQP4, that is particularly rich in the central nervous system, is more efficient in water conduction and more temperature-sensitive than other water-only channels (excluding glycerol channels that also conduct water when not inhibited by glycerol).