Mechanisms of selectivity in channels and enzymes studied with interactive molecular dynamics
Mechanisms of selectivity in channels and enzymes studied with interactive molecular dynamics
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DOI：
10.1016/s0006-3495(03)74452-x
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Grayson, P;Tajkhorshid, E;Schulten, K
交互式分子动力学，一个新的建模工具，在原子水平上的生物过程的物理机制的快速调查，适用于研究的选择性和调节的膜通道蛋白GlpF和甘油激酶的酶。这些蛋白促进大肠杆菌甘油代谢的前两步。尽管它们的不同功能和架构的蛋白质被发现采用共同的机制为底物的选择性：诱导的几何拟合结构同源的结合位点和诱导的快速偶极矩反转。在这两种蛋白质中与水竞争氢键结合位点对于底物运动是至关重要的。在甘油激酶，它表明，拟议的域运动防止与水的竞争，反过来调节甘油的结合。
Interactive molecular dynamics, a new modeling tool for rapid investigation of the physical mechanisms of biological processes at the atomic level, is applied to study selectivity and regulation of the membrane channel protein GlpF and the enzyme glycerol kinase. These proteins facilitate the first two steps of Escherichia coli glycerol metabolism. Despite their different function and architecture the proteins are found to employ common mechanisms for substrate selectivity: an induced geometrical fit by structurally homologous binding sites and an induced rapid dipole moment reversal. Competition for hydrogen bonding sites with water in both proteins is critical for substrate motion. In glycerol kinase, it is shown that the proposed domain motion prevents competition with water, in turn regulating the binding of glycerol.