Large-scale simulations of ribosomal decoding

 描述（由申请人提供）：更高分辨率的冷冻电子显微镜和真核核糖体结构的出现为核糖体机制领域开辟了广阔的可能性。与Christian Spahn cryo-EM实验室一起，我们最近发表了人类核糖体在与解码相关的各种功能状态下的第一个全原子模型。使用我们的MDfit方法，我们产生了与cryo-EM密度高度一致的模型。这项研究揭示了真核生物特有的一种新的构象变化：亚基卷曲。我们还对tRNA进入细菌核糖体进行了广泛的研究。在这里，我们将研究亚基滚动的哺乳动物核糖体解码过程中的住宿的影响。我们还将研究解码前和调节后发生的构象变化。通过对人与细菌核糖体作用机制的比较，我们希望能对抗生素的作用机制有更深入的了解。我们将结合使用明确的溶剂和所有原子减少描述技术，根据我们以前的出版物。我们还将扩展我们的MDfit技术，以获得更高分辨率的cryo-EM密度。

 DESCRIPTION (provided by applicant): The advent of higher resolution cryo electron microscopy and structures of eukaryotic ribosomes has opened the field of ribosome mechanism to a vast array of possibilities. Together with the Christian Spahn cryo-EM lab, we recently published one of the first all-atom models of the human ribosome in various functional states related to decoding. Using our MDfit method, we produced models highly consistent with cryo-EM density. The study revealed a new conformational change specific to eukaryotes: subunit rolling. We have also performed extensive studies on tRNA accommodation into the bacterial ribosome. Here, we will investigate the effect of subunit rolling on accommodation during decoding by the mammalian ribosome. We will also study conformational changes occurring prior to decoding and after accommodation. By comparing human and bacterial ribosome mechanism, we hope to gain insight into antibiotic action mechanism. We will use a combination of explicit solvent and all-atom reduced description techniques based on our previous publications. We will also extend our MDfit technique for higher resolution cryo-EM density.