Conformational equilibria and free energy profiles for the allosteric transition of the ribose-binding protein
Conformational equilibria and free energy profiles for the allosteric transition of the ribose-binding protein
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DOI：
10.1016/j.jmb.2005.08.009
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发表时间：
2005-10-14
影响因子：
5.6
通讯作者：
Levy, RM
中科院分区：
文献类型：
--
作者：
Ravindranathan, KP;Gallicchio, E;Levy, RM
核糖结合蛋白（RBP）是一种糖结合细菌周质蛋白，其功能与结合核糖后从开放构象到闭合构象的大的变构构象变化有关。求解了RBP在开、闭构象下的晶体结构。有人假设，开放和封闭的构象存在于溶液中的动态平衡，和糖结合的人口从开放的构象转变为封闭的构象。在这里，我们通过计算机模拟研究伴随着这种构象变化的热力学变化，并模拟伴随着变构转变的结构变化，使用伞形采样分子动力学和加权直方图分析方法。开放状态由不同的构象集合组成;开放的无核糖X射线晶体构象是该集合的代表。RBP的未连接的开放形式通过构象熵来稳定。模拟预测可检测的人口封闭的无核糖构象在溶液中。额外的域间氢键稳定这种状态。预测的平衡从开放到封闭状态的结合核糖的转变与实验一致。这是由核糖-蛋白质相互作用引起的闭合构象的能量稳定所驱动的。我们还观察到一个迄今未观察到的核糖结合部分开放状态的显着人口。我们相信，这种状态是一个已被建议发挥作用的核糖转移到膜结合的通透酶复合物。(c)2005爱思唯尔有限公司保留所有权利。
The ribose-binding protein (RBP) is a sugar-binding bacterial periplasmic protein whose function is associated with a large allosteric conformational change from an open to a closed conformation upon binding to ribose. The crystal structures of RBP in open and closed conformations have been solved. It has been hypothesized that the open and closed conformations exist in a dynamic equilibrium in solution, and that sugar binding shifts the population from open conformations to closed conformations. Here, we study by computer simulations the thermodynamic changes that accompany this conformational change, and model the structural changes that accompany the allosteric transition, using umbrella sampling molecular dynamics and the weighted histogram analysis method. The open state is comprised of a diverse ensemble of conformations; the open ribose-free X-ray crystal conformations being representative of this ensemble. The unligated open form of RBP is stabilized by conformational entropy. The simulations predict detectable populations of closed ribose-free conformations in solution. Additional interdomain hydrogen bonds stabilize this state. The predicted shift in equilibrium from the open to the closed state on binding to ribose is in agreement with experiments. This is driven by the energetic stabilization of the closed conformation due to ribose-protein interactions. We also observe a significant population of a hitherto unobserved ribose-bound partially open state. We believe that this state is the one that has been suggested to play a role in the transfer of ribose to the membrane-bound permease complex. (c) 2005 Elsevier Ltd. All rights reserved.