Constrained Multiple Structure Feature Alignment (CMSFA)

Abstract

With the rapid accumulation of released threedimensional protein structure database, the importance of structural comparison parallels that of sequence alignment. It has been shown that despite primary sequence diversity, protein structures of related sequences possess a structural core of α- helices and β-sheets and vary in the loop regions. To determine the characteristic properties for each target sequence from a protein family, we have developed a fast algorithm for structure alignment based on the combination of primary sequences and three-dimensional structures. The sequence-based comparison utilizes the labeled consensus motifs to provide combinatorial features for multiple sequence alignment, and the spatial positions of the key amino acids in each of the combinational segments are assigned for the proposed constrained multiple structure feature alignment (CMSFA). The 3D coordinates of aligned amino acids provide data for calculating the root-mean-square deviation (RMSD) values which build the references for the detection of structurally distinct regions. In this study, RNase A P450, and ricin A protein families were employed to demonstrate the outstanding performance of the structure alignment algorithms, and the comparisons between our proposed CMSFA and several existing structural alignment tools are also described in this paper.