Origins of proton transport behavior from selectivity domain mutations of the aquaporin-1 channel
Origins of proton transport behavior from selectivity domain mutations of the aquaporin-1 channel
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DOI：
10.1529/biophysj.106.084061
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发表时间：
2006-05-01
影响因子：
3.4
通讯作者：
Voth, GA
中科院分区：
文献类型：
--
作者：
Chen, HN;Wu, YJ;Voth, GA
采用分子动力学模拟和Poisson-Nernst-Planck理论计算了水通道蛋白1（AQP 1）突变体（H180 A/R195 V、H180 A和R195 V）质子沿着通道的渗透自由能分布和最大离子电导。质子动力学采用多状态经验价键模型（MS-EVB）描述。结果揭示了三个主要贡献的整体自由能势垒质子运输在AQP 1：1），双极场，2），静电排斥由于Arg-195残基，和3），脱水惩罚由于狭窄的通道孔。双突变（H180 A/R195 V）通过同时松弛直接静电相互作用（通过R195 V）和脱水效应（通过H180 A），使总自由能垒急剧下降约20 kcal/mol。
The permeation free-energy profile and maximum ion conductance of proton transport along the channel of three aquaporin-1 (AQP1) mutants (H180A/R195V, H180A, and R195V) are calculated via molecular dynamics simulations and Poisson-Nernst-Planck theory. The proton dynamics was described by the multistate empirical valence bond (MS-EVB) model. The results reveal three major contributions to the overall free-energy barrier for proton transport in AQP1: 1), the bipolar field, 2), the electrostatic repulsion due to the Arg-195 residue, and 3), the dehydration penalty due to the narrow channel pore. The double mutation ( H180A/R195V) drastically drops the overall free-energy barrier by roughly 20 kcal/mol via simultaneously relaxing the direct electrostatic interaction ( by R195V) and dehydration effect ( by H180A).