Abstract：
We construct and analyze disconnectivity graphs to provide the first graphical representation of the vibrational energy landscape of a protein, in this study β2AR, a G-protein coupled receptor (GPCR), in active and inactive states. The graphs, which indicate the relative free energy of each residue and the minimum free energy barriers for energy transfer between them, reveal important composition, structural and dynamic properties that mediate the flow of energy. Prolines and glycines, which contribute to GPCR plasticity and function, are identified as bottlenecks to energy transport along the backbone from which alternative pathways for energy transport via nearby noncovalent contacts emerge, seen also in the analysis of first passage time (FPT) distributions presented here. Striking differences between the disconnectivity graphs and FPT distributions for the inactive and active states of β2AR are found where structural and dynamic changes occur upon activation, contributing to allosteric regulation.
摘要：
我们构建和分析不连通性图，以提供蛋白质振动能量景观的第一个图形表示，在这项研究中β2AR，G蛋白偶联受体（GPCR），处于活动状态和非活动状态。这些图表，表示每个残基的相对自由能以及它们之间能量转移的最小自由能垒，揭示重要的成分，调节能量流动的结构和动态特性。脯氨酸和甘氨酸，这有助于GPCR的可塑性和功能，被确定为沿着骨架的能量传输的瓶颈，通过附近的非共价接触出现了能量传输的替代途径，在此处介绍的首次通过时间（FPT）分布分析中也可以看到。发现β2AR的非活动状态和活动状态的不连通性图和FPT分布之间存在惊人的差异，其中激活时会发生结构和动态变化，有助于变构调节。
