Ilan Boaz, Tajkhorshid Emad, Schulten Klaus, Voth Gregory A
Department of Chemistry and Henry Eyring Center for Theoretical Chemistry, University of Utah, Salt Lake City, Utah 84112-0850, USA.
Proteins. 2004 May 1;55(2):223-8. doi: 10.1002/prot.20038.
The mechanism of proton exclusion in aquaporin channels is elucidated through free energy calculations of the pathway of proton transport. The second generation multistate empirical valence bond (MS-EVB2) model was applied to simulate the interaction of an excess proton with the channel environment. Jarzynski's equality was employed for rapid convergence of the free energy profile. A barrier sufficiently high to block proton transport is located near the channel center at the NPA motif-a site involved in bi-orientational ordering of the embedded water-wire in absence of the excess proton. A second and lower barrier is observed at the selectivity filter near the periplasmic outlet where the channel is narrowest. This secondary barrier may be essential in filtering other large solutes and cations.
通过对质子传输途径的自由能计算，阐明了水通道蛋白通道中质子排斥的机制。应用第二代多态经验价键（MS-EVB2）模型来模拟过量质子与通道环境的相互作用。利用雅津斯基等式实现自由能分布的快速收敛。在通道中心附近的NPA基序处发现了一个足以阻止质子传输的高势垒，该位点在没有过量质子的情况下参与嵌入水线的双取向排列。在靠近周质出口的选择性过滤器处，即通道最窄的地方，观察到第二个较低的势垒。这个二级势垒可能在过滤其他大溶质和阳离子方面至关重要。
