Abstract：
The effects of amino acid insertions and deletions (InDels) remain a rather under-explored area of structural biology. These variations oftentimes are the cause of numerous disease phenotypes. In spite of this, research to study InDels and their structural significance remains limited, primarily due to a lack of experimental information and computational methods. In this work, we fill this gap by modeling InDels computationally; we investigate the rigidity differences between the wildtype and a mutant variant with one or more InDels. Further, we compare how structural effects due to InDels differ from the effects of amino acid substitutions, which are another type of amino acid mutation. We finish by performing a correlation analysis between our rigidity-based metrics and wet lab data for their ability to infer the effects of InDels on protein fitness.
摘要：
氨基酸插入和缺失（InDels）的影响仍然是结构生物学中尚未充分探索的领域。这些变异常常是许多疾病表型的原因。尽管如此,研究InDels及其结构意义的研究仍然有限，主要是由于缺乏实验信息和计算方法。在这项工作中,我们通过对InDels进行计算建模来填补这一空白；我们研究了野生型与具有一个或多个InDels的突变变体之间的刚性差异。Further,我们比较了InDels的结构效应与氨基酸取代的效应有何不同，是另一种类型的氨基酸突变。我们通过在基于刚性的指标和湿实验室数据之间进行相关性分析来推断InDels对蛋白质适应性的影响。
