Molecular evolution of ion channels: Amino acid sequences and 3D structures

Abstract

Comparative analysis of structure and function of macromolecules, such as proteins, is an integral part of modern evolutionary biology. The first and critical step in understanding evolution of homologous proteins is their amino acid sequence alignment. However, standard algorithms fail to provide unambiguous sequence alignment for proteins of poor homology. More reliable results can be provided by comparing experimental 3D structures obtained at atomic resolution with the aid of X-ray structural analysis. If such structures are lacking, homology modeling is used which considers indirect experimental data on functional roles of individual amino acid residues. An important problem is that sequence alignment, which reflects genetic modifications, not necessarily corresponds to functional homology, which depends on 3D structures critical for natural selection. Since the alignment techniques relying only on the analysis of primary structures carry no information on the functional properties of proteins, the inclusion of 3D structures into consideration is of utmost importance. Here we consider several ion channels as examples to demonstrate that alignment of their 3D structures can significantly improve sequence alignment obtained by traditional methods.