Progressive combinatorial algorithm for multiple structural alignments: Application to distantly related proteins

Abstract

MALECON is a progressive combinatorial procedure for multiple alignments of protein structures. It searches a library of pairwise alignments for all three-protein alignments in which a specified number of residues is consistently aligned. These alignments are progressively expanded to include additional proteins and more spatially equivalent residues, subject to certain criteria. This action involves superimposing the aligned proteins by their hitherto equivalent residues and searching for additional Calpha atoms that lie close in space. The performance of MALECON is illustrated and compared with several extant multiple structure alignment methods by using as test the globin homologous superfamily, the OB and the Jellyrolls folds. MALECON gives better definitions of the common structural features in the structurally more diverse proteins of the OB and Jellyrolls folds, but it yields comparable results for the more similar globins. When no consistent multiple alignments can be derived for all members of a protein group, our procedure is still capable of automatically generating consistent alignments and common core definitions for subgroups of the members. This finding is illustrated for proteins of the OB fold and SH3 domains, believed to share common structural features, and should be very instrumental in homology modeling and investigations of protein evolution.

Multiple Structure Alignment by Optimal RMSD Implies That the Average Structure Is a Consensus

“…Examples from the literature include the sum of all pairwise squared distances 7,8 , which we also use, or the average RMSD per aligned position 9 . If we consider the protein structures as rigid bodies, then problem of multiple structure alignment is to translate and rotate these structures to minimize the score function.…”

“…Gerstein and Levitt 10 choose the structure that has minimum total RMSD to all other structures as the consensus structure and aligns other structures to it. Ochagavia and Wodak 9 and Lupyan et al 7 present a progressive algorithm that chooses one structure at a time and minimizes the total RMSD to all the already aligned structures until all the structures are aligned. Other researchers use nondeterministic methods.…”

Evaluation of Novel Protein Structure Comparison Algorithms Based on Objective Function Rankings

“…Set 1 contains closely related group of mammalian data while set 2 contains a more widely diverged set. Set 3 includes three additional sets, and finally set 4 has 15 sets which were described in previous work [17].…”

A Relational Extension of the Notion of Motifs: Application to the Common 3D Protein Substructures Searching Problem

“…Some well known pairwise structural alignment methods have been adapted to multiple structural alignment. For example CE-MC (Guda et al, 2001) is an adaptation of CE (Shindyalov and Bourne, 1998), POSA (Ye and Godzik, 2005) of FATCAT (Ye and Godzik, 2003), and MALECON (Ochagavia and Wodak, 2004) of Boutonnet et al algorithm (Boutonnet et al, 1995). The methods COMPARER (Sali and Blundell, 1990), MATRAS (Kawabata, 2003) and MAMMOTH (Ortiz et al, 2002;Lupyan et al, 2005) have also been adapted to multiple structural alignment.…”