Noel Jeffrey K, Chahine Jorge, Leite Vitor B P, Whitford Paul Charles
Center for Theoretical Biological Physics, Rice University, Houston, Texas.
Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, Brazil.
Biophys J. 2014 Dec 16;107(12):2881-2890. doi: 10.1016/j.bpj.2014.10.022.
To reveal the molecular determinants of biological function, one seeks to characterize the interactions that are formed in conformational and chemical transition states. In other words, what interactions govern the molecule's energy landscape? To accomplish this, it is necessary to determine which degrees of freedom can unambiguously identify each transition state. Here, we perform simulations of large-scale aminoacyl-transfer RNA (aa-tRNA) rearrangements during accommodation on the ribosome and project the dynamics along experimentally accessible atomic distances. From this analysis, we obtain evidence for which coordinates capture the correct number of barrier-crossing events and accurately indicate when the aa-tRNA is on a transition path. Although a commonly used coordinate in single-molecule experiments performs poorly, this study implicates alternative coordinates along which rearrangements are accurately described as diffusive movements across a one-dimensional free-energy profile. From this, we provide the theoretical foundation required for single-molecule techniques to uncover the energy landscape governing aa-tRNA selection by the ribosome.
为了揭示生物学功能的分子决定因素，人们试图表征在构象和化学过渡态中形成的相互作用。换句话说，是什么相互作用支配着分子的能量格局？为了实现这一点，有必要确定哪些自由度能够明确识别每个过渡态。在这里，我们对核糖体容纳过程中大规模氨酰基转移RNA（aa-tRNA）重排进行了模拟，并沿着实验可及的原子距离投影动力学。通过该分析，我们获得了证据，证明哪些坐标捕捉到了正确数量的势垒穿越事件，并准确指示了aa-tRNA何时处于过渡路径上。尽管单分子实验中常用的坐标表现不佳，但本研究表明，沿着这些替代坐标，重排可被准确描述为跨越一维自由能分布的扩散运动。由此，我们为单分子技术揭示核糖体选择aa-tRNA的能量格局提供了所需的理论基础。
