An improved algorithm for estimation of residue evolutionary conservation

Evolutionary conservation estimated from a multiple sequence alignment is a powerful indicator of the functional significance of a residue, and helps to predict active sites, ligand binding sites, and protein interaction interfaces. Many algorithms that calculate conservation work well provided better and balanced alignment are used. Such a strong dependence on the alignment makes the results highly variable. Mihalek et al [1] introduced a class of hybrid methods to estimate the residue evolutionary conservation. Here, we propose an improved algorithm handling the gap in the multi-sequences alignment to compute the residue conservation scores. Comparing with Mihalek's and Ben-Tal's ConSurf methods, the results of simulation show that our methods are effective and increase the sensitivity and specificity of prediction, as well as make the conservation prediction algorithm more robust.