论文标题
共价配体抑制人蛋白酶体的原子模拟
Atomistic simulations of the human proteasome inhibited by a covalent ligand
论文作者
论文摘要
蛋白酶体是导致蛋白质降解的大型生物分子络合物。由于其在细胞稳态中的基本作用以及药物应用的巨大潜力，因此它正在受到强烈的研究。 X射线晶体学和冷冻电子显微镜的最新数据表明，抑制剂结合后存在大规模的结构变化。我们对天然和抑制蛋白酶体进行了原子分子动力学模拟，以了解抑制的分子细节。在这里，我们描述了模拟的技术细节，并评估获得的轨迹的质量。蛋白酶体的生化方面正在进一步研究，并将在其他地方发表。这项工作是HLR的GCS-Prot项目的一部分，在Cray XC40超级计算系统上运行。
The proteasome is a large biomolecular complex responsible for protein degradation. It is under intense research due to its fundamental role in cellular homeostasis, and tremendous potential for medicinal applications. Recent data from X-ray crystallography and cryo-electron microscopy have suggested that there is a large-scale structural change upon binding of an inhibitor. We carried out atomistic molecular dynamics simulations of the native and inhibited proteasomes to understand the molecular details of the inhibition. Here we describe the technical details of the simulations and assess the quality of the trajectories obtained. The biochemical aspects of the proteasome are under further investigation and will be published elsewhere. This work was a part of the GCS-Prot project at the HLRS, run on the Cray XC40 supercomputing system.
