Assessing the effects of amino acid insertion and deletion mutations

Alistair Turcan, Filip Jagodzinski

Abstract:

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.