Conformational Transition Pathways Explored by Monte Carlo Simulation Integrated with Collective Modes
Conformational Transition Pathways Explored by Monte Carlo Simulation Integrated with Collective Modes
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DOI：
10.1529/biophysj.107.128447
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发表时间：
2008-12-15
影响因子：
3.4
通讯作者：
Doruker, Pemra
中科院分区：
文献类型：
--
作者：
Kantarci-Carsibasi, Nigar;Haliloglu, Turkan;Doruker, Pemra
蛋白质在开放/闭合或自由/结合状态之间的构象转变具有重要的功能。我们提出了一种技术，其中从各向异性网络模型(ANM)获得的集体模结合蒙特卡罗(MC)模拟方法来研究构象转变路径和路径中间体。将ANM-MC技术应用于腺苷酸激酶(AK)和血红蛋白。在模拟过程中，简正波不断更新的迭代方法成功地完成了AK的开闭构象和紧张松弛形式的血红蛋白之间的转换(两个末端结构之间的C-α均方根偏差分别为7.13埃和3.55埃)。对于AK和Hb，目标构象的均方根偏差分别为2.27埃和1.90埃。中间构象与AK家族的晶体结构在3.0埃的均方根偏差内重叠。在血红蛋白的情况下，从紧张到放松的转变经历了放松状态。在这两种情况下，最低频率模式在转换期间都是有效的。采用目标蒙特卡罗方法，不使用集体模式。ANM-MC和目标蒙特卡罗技术都可以通过有效而现实的构象搜索来探索转变路径中的事件序列。
Conformational transitions between open/closed or free/bound states in proteins possess functional importance. We propose a technique in which the collective modes obtained from an anisotropic network model (ANM) are used in conjunction with a Monte Carlo (MC) simulation approach, to investigate conformational transition pathways and pathway intermediates. The ANM-MC technique is applied to adenylate kinase (AK) and hemoglobin. The iterative method, in which normal modes are continuously updated during the simulation, proves successful in accomplishing the transition between open-closed conformations of AK and tense-relaxed forms of hemoglobin (C-alpha - root mean square deviations between two end structures of 7.13 angstrom and 3.55 angstrom, respectively). Target conformations are reached by root mean-square deviations of 2.27 angstrom and 1.90 angstrom for AK and hemoglobin, respectively. The intermediate conformations overlap with crystal structures from the AK family within a 3.0-angstrom root mean-square deviation. In the case of hemoglobin, the transition of tense-to-relaxed passes through the relaxed state. In both cases, the lowest-frequency modes are effective during transitions. The targeted Monte Carlo approach is used without the application of collective modes. Both the ANM-MC and targeted Monte Carlo techniques can explore sequences of events in transition pathways with an efficient yet realistic conformational search.