The bacterial ribosomal tunnel is equipped with numerous sites highly sensitive to the course of the translation process. This study investigates allosteric pathways linking distant functional sites that collaboratively play a role either in translation regulation or recruitment of chaperones. We apply perturbation response scanning (PRS) analysis to 700 ns long and 500 ns long coarse-grained molecular dynamics simulations of E. coli and T. thermophilus large subunits, respectively, to reveal nucleotides/residues with the ability to transmit perturbations by dynamic rationale. We also use the residue network model with the k-shortest pathways method to calculate suboptimal pathways based on the contact topology of the ribosomal tunnel of E. coli crystal structure and 101 ClustENM generated conformers of T. thermophilus large subunit. In the upper part of the tunnel, results suggest that A2062 and A2451 can communicate in both directions for translation stalling, mostly through dynamically coupled C2063, C2064, and A2450. For a similar purpose, U2585 and U2586 are coupled with A2062, while they are also sensitive to uL4 and uL22 at the constriction region through two different pathways at the opposite sides of the tunnel wall. In addition, the constriction region communicates with the chaperone binding site on uL23 at the solvent side but through few nucleotides. Potential allosteric communication pathways between the lower part of the tunnel and chaperone binding site mostly use the flexible loop of uL23, while A1336–G1339 provide a suboptimal pathway. Both species seem to employ similar mechanisms in the long tunnel, where a non-conserved cavity at the bacterial uL23 and 23S rRNA interface is proposed as a novel drug target.

细菌核糖体通道配备了许多对翻译过程高度敏感的位点。这项研究调查了相互联系的遥远功能位点的变构途径，这些功能位点在翻译调控或伴侣的募集中共同发挥作用。我们将扰动响应扫描（PRS）分析应用于700 ns长和500 ns长的粗颗粒分子动力学模拟大肠杆菌 和 嗜热链球菌大亚基，分别揭示具有通过动态原理传递扰动的能力的核苷酸/残基。我们还将残差网络模型与ķ最短路径的方法基于核糖体隧道的接触拓扑计算次优路径 大肠杆菌 的晶体结构和101 ClustENM生成的构象异构体 嗜热链球菌大亚基。在隧道的上部，结果表明A2062和A2451可以在两个方向上进行通信以进行翻译停顿，主要是通过动态耦合的C2063，C2064和A2450。出于类似的目的，U2585和U2586与A2062耦合，同时它们也通过在隧道壁相对侧的两条不同路径对收缩区域的uL4和uL22敏感。此外，收缩区在溶剂侧与uL23上的伴侣结合位点连通，但仅通过少数核苷酸。隧道下部和伴侣结合位点之间的潜在变构通讯途径主要使用uL23的柔性环，而A1336–G1339提供了次佳的途径。两种物种在长隧道中似乎都采用类似的机制，