Su Ji Guo, Han Xiao Ming, Zhang Xiao, Hou Yan Xue, Zhu Jian Zhuo, Wu Yi Dong
a College of Science , Yanshan University , Qinhuangdao 066004 , Hebei Province , China.
J Biomol Struct Dyn. 2016;34(3):560-71. doi: 10.1080/07391102.2015.1044910. Epub 2015 Jun 5.
Protein collective motions play a critical role in many biochemical processes. How to predict the functional motions and the related key residue interactions in proteins is important for our understanding in the mechanism of the biochemical processes. Normal mode analysis (NMA) of the elastic network model (ENM) is one of the effective approaches to investigate the structure-encoded motions in proteins. However, the motion modes revealed by the conventional NMA approach do not necessarily correspond to a specific function of protein. In the present work, a new analysis method was proposed to identify the motion modes responsible for a specific function of proteins and then predict the key residue interactions involved in the functional motions by using a perturbation approach. In our method, an internal coordinate that accounts for the specific function was introduced, and the Cartesian coordinate space was transformed into the internal/Cartesian space by using linear approximation, where the introduced internal coordinate serves as one of the axes of the coordinate space. NMA of ENM in this internal/Cartesian space was performed and the function-relevant motion modes were identified according to their contributions to the specific function of proteins. Then the key residue interactions important for the functional motions of the protein were predicted as the interactions whose perturbation largely influences the fluctuation along the internal coordinate. Using our proposed methods, the maltose transporter (MalFGK2) from E. Coli was studied. The functional motions and the key residue interactions that are related to the channel-gating function of this protein were successfully identified.
蛋白质的集体运动在许多生化过程中起着关键作用。如何预测蛋白质中的功能运动以及相关的关键残基相互作用，对于我们理解生化过程的机制非常重要。弹性网络模型（ENM）的正常模式分析（NMA）是研究蛋白质中结构编码运动的有效方法之一。然而，传统NMA方法揭示的运动模式不一定对应于蛋白质的特定功能。在本工作中，提出了一种新的分析方法，通过使用微扰方法来识别负责蛋白质特定功能的运动模式，然后预测功能运动中涉及的关键残基相互作用。在我们提出的方法中，引入了一个考虑特定功能的内部坐标，并通过线性近似将笛卡尔坐标空间转换为内部/笛卡尔空间，其中引入的内部坐标作为坐标空间的轴之一。在这个内部/笛卡尔空间中对ENM进行NMA，并根据它们对蛋白质特定功能的贡献来识别与功能相关的运动模式。然后，将对蛋白质功能运动重要的关键残基相互作用预测为其微扰在很大程度上影响沿内部坐标波动的相互作用。使用我们提出的方法，对来自大肠杆菌的麦芽糖转运蛋白（MalFGK2）进行了研究。成功识别了与该蛋白质通道门控功能相关的功能运动和关键残基相互作用。
