Assessing the Effects of Amino Acid Insertion and Deletion Mutations

Despite being a recurring type of sequence variation, amino acid insertions and deletions (InDels) and their resulting functional significance remain a rather unexplored area of structural biology. InDels are quite often the driving force behind many diseases. Despite that, modeling InDels and exploring their functional implications remains lacking, mainly due to the dearth of experimental information and computational methodologies. In this work we introduce an algorithmic approach to model short InDels in silico and explore the structural and rigidity differences between the wildtype and the mutant protein structures. We assess rigidity to gather useful information about the protein’s general structure, the location of flexible and rigid clusters, and to permit a visual analysis of the effects of InDels local to the mutation site. Our results show that our method can efficiently create a computer-generated mutant that is functionally similar to the experimental mutant at both the local region of the InDel, as well as on the entire protein scale. The results show promise in our ability to accurately predict the effects of short insertions and deletions on the structural properties of proteins.