Ko Youn Jo, Huh June, Jo Won Ho
School of Materials Science and Engineering and Hyperstructured Organic Materials Research Center, Seoul National University, Seoul 151-742, Korea.
Proteins. 2008 Mar;70(4):1442-50. doi: 10.1002/prot.21696.
Although the mechanism of proton exclusion in aquaporin is investigated by many researchers, the detailed molecular mechanism for ion exclusion in aquaporin is still not completely understood. In the present work, a detailed mechanism for ion exclusion in aquaporin-1 (AQP1) at an atomistic level is investigated by calculating the free energy for transport of ions in AQP1 using an atomistic molecular dynamics simulation. For this purpose, sodium and chloride ions are chosen as representatives for nonprotonic ions. The simulation shows that the free energy barrier showing its maximum is located at the NPA region for sodium ion while it is located at both the front and the rear for chloride ion and that the barrier height is 18 and 9 kcal/mol, respectively, indicating that the ions are not able to pass through aquaporin. Analysis of the pair interaction energy between the permeating ion and its environment reveals that sodium ion is excluded by the positive charge generated by two alpha-helical macro-dipoles, while chloride ion is expelled by carbonyl oxygen atoms protruding from pore-making residues before it reaches the NPA motif. It is also found that the number of water molecules hydrating the ions is reduced as the ions enter the pore, implying that the energetic cost for detaching water molecules from a permeating ion also contributes to the free energy barriers of ion transport in AQP1.
尽管许多研究人员对水通道蛋白中质子排斥的机制进行了研究，但水通道蛋白中离子排斥的详细分子机制仍未完全理解。在本工作中，通过使用原子分子动力学模拟计算离子在水通道蛋白-1（AQP1）中传输的自由能，研究了原子水平上AQP1中离子排斥的详细机制。为此，选择钠离子和氯离子作为非质子离子的代表。模拟表明，显示最大值的自由能垒对于钠离子位于NPA区域，而对于氯离子则位于前后两端，且垒高分别为18和9千卡/摩尔，这表明离子无法穿过水通道蛋白。对渗透离子与其环境之间的对相互作用能的分析表明，钠离子被两个α-螺旋大偶极产生的正电荷排斥，而氯离子在到达NPA基序之前被造孔残基突出的羰基氧原子排出。还发现，随着离子进入孔道，与离子水合的水分子数量减少，这意味着从渗透离子上分离水分子的能量成本也对AQP1中离子传输的自由能垒有贡献。
