Analysis of insertions/deletions in protein structures

Investigating protein structural plasticity by surveying the consequence of an amino acid deletion from TEM‐1 β‐lactamase

“…Together with substitutions, the insertion or deletion (known as indels) of amino acids constitute major mutational mechanisms observed during divergent evolution [3,4]. This is highlighted by length variations that are routinely observed in comparisons of homologous proteins.…”

“…Nonetheless, mutations that remove an amino acid from the polypeptide are generally expected to be detrimental to proteins due to the anticipated major local and global structural changes, including register shifts in regular secondary structure elements, required to accommodate the removal of a residue. Therefore, long flexible loops are considered the places most likely to tolerate a deletion [3]. However, analysis of several specific deletion mutants of T4 lysozyme [8], the B1 domain of protein G [9] and Ricin A-chain [10] suggests this is not always the case.…”

Homology Modeling: Generating Structural Models to Understand Protein Function and Mechanism

“…One way to align structure to sequence can be to match the structureprofile of the template (amino acid propensities in each position of the fold) to the sequence-profile of the query (amino acid propensities at each position of the sequence based on evolution) using dynamic programming, with the gap-penalties at each template position set by the secondary structure at that position. It has been observed that insertions and deletions (which arise due to gaps in alignments) are minimal in positions that feature helix or strand [37], hence gap penalties can be set higher at positions in the template featuring helix or strand. Similarly, predictions for buried and exposed positions of the query sequence have also been used in sequencestructure alignments.…”

The insertion of palindromic repeats in the evolution of proteins

“…Globular proteins exhibit a compact hydrophobic core and relatively flexible surface loops. The latter are known to be much more tolerant to evolutionary changes than the protein core [22]. Experimental insertions of 7-17 residues into a loop of the chymotrypsin inhibitor-2 (64 amino acids) has little effect on protein stability and folding rate [23].…”

“…The majority (93%) of the insertions and/or deletions identified in contemporary protein sequences are shorter than 10 residues [22]. However, this estimate is computed from the most reliable portions of sequence alignments (i.e.…”