论文标题
柔性蛋白质结构的蒙特卡洛采样：应用于SARS-COV-2 OMICRON变体
Monte Carlo sampling of flexible protein structures: an application to the SARS-CoV-2 omicron variant
论文作者
论文摘要
蛋白质在执行功能时可以表现出动态的结构柔韧性，尤其是在与其他分子相互作用的结合区域中。对于促进COVID-19感染的关键SARS-COV-2尖峰蛋白，研究以前已经确定了几个具有治疗意义的高度灵活区域。但是，蛋白质数据库中可用的蛋白质结构被称为静态快照，可能无法充分描述这种灵活性，此外，这些快照无法与新的突变和变体保持同步。在本文中，我们提出了一种根据给定能量函数的玻尔兹曼分布，用于宽阔采样蛋白质结构的3-D构象空间。我们的方法与以前的抽样方法不同，该方法侧重于找到预测单个稳定结构的最低能量构象。我们在SARS-COV-2 OMICRON变体上说明了我们的方法作为及时的兴趣。我们的结果将序列位置495-508确定为OMICRON突变对可能构象空间的影响最大的关键区域，这与其他初步研究的发现有关Omicron变体的结合特性的发现。
Proteins can exhibit dynamic structural flexibility as they carry out their functions, especially in binding regions that interact with other molecules. For the key SARS-CoV-2 spike protein that facilitates COVID-19 infection, studies have previously identified several such highly flexible regions with therapeutic importance. However, protein structures available from the Protein Data Bank are presented as static snapshots that may not adequately depict this flexibility, and furthermore these cannot keep pace with new mutations and variants. In this paper we present a sequential Monte Carlo method for broadly sampling the 3-D conformational space of protein structure, according to the Boltzmann distribution of a given energy function. Our approach is distinct from previous sampling methods that focus on finding the lowest-energy conformation for predicting a single stable structure. We exemplify our method on the SARS-CoV-2 omicron variant as an application of timely interest. Our results identify sequence positions 495-508 as a key region where omicron mutations have the most impact on the space of possible conformations, which coincides with the findings of other preliminary studies on the binding properties of the omicron variant.
