Structure and function analysis of flexible alignment regions in proteins

Abstract

BackgroundProtein structural alignment plays a key role in defining gold standards for a variety of bioinformatics applications. These include homology assessment, phylogenetic tree construction and multiple sequence alignment evaluation.Our recent findings [1] however showed that superposition methods are rather sensitive to structural variation. To sidestep the problem of alignment variability, golden standards are often derived from the more conserved and 'trusted' regions. It therefore remains unclear which Figure 1 Structure and function analysis of alignment variability by means of the standard deviation of residue shifts over an ensemble of alternate alignments (sigma). (A) Shows the fraction of helical residues increasing with higher variability at the cost of the fraction of coil residues. (B) Shows the even distribution of functional sites (as grouped by Prosite) over a large range of variability.

Highlights from the 5th International Society for Computational Biology Student Council Symposium at the 17th Annual International Conference on Intelligent Systems for Molecular Biology and the 8th European Conference on Computational Biology

“…There are several factors that influence variability in structural alignments. Pirovano et al [ 9 ] determined that certain types of folds (helices and coils) are usually observed in inconsistent alignment regions. Since this observation is at odds with currently used alignment strategies, more care should be taken in the development of new algorithms.…”