| Popis: |
The increasing number of available protein structures requires efficient tools for protein structure comparison. Indeed, pairwise and multiple structural alignments are essential for the analysis of function, evolution and architecture of protein structures. We have developed methods for pairwise and multiple structure comparisons largely based on sequence alignment techniques. A widely used Structural Alphabet named Protein Blocks (PBs) was used to transform the information on 3D protein backbone conformation as a 1D sequence string. A sequence alignment procedure based on dynamic programming was developed and named iPBA. The main adaptations of the procedure consist in using a dedicated PB Substitution Matrix, by weighting local similar stretches and by coupling linearly amino acid substitutions scores with PB substitutions. The resulting pairwise alignments were compared with DALI and MUSTANG and showed a significant improvement in 81.3% of the cases (Joseph, Srinivasan, de Brevern, Biochimie, 2011). A progressive alignment strategy similar to CLUSTALW was adopted for multiple PB sequence alignment, namely mulPBA. Highly similar stretches identified by the pairwise alignments are favored by higher weights during the alignment. The residue equivalences from PB based alignments are used to obtain a 3D-fit of the structures followed by an iterative refinement of the structural superposition. The method was benchmarked on different datasets used by similar approaches. The alignment quality is better than with MULTIPROT, MUSTANG and those within HOMSTRAD, in more than 85% of the cases. Comparison with other rigid-body and flexible approaches demonstrate that mulPBA alignments are superior to most rigid-body approaches and highly comparable to flexible alignment methods (Joseph, Srinivasan, de Brevern, Biochimie, 2012). These methods are implemented in two dedicated web servers (Gelly, Joseph, Srinivasan, de Brevern, Nucl Acid Res, 2011; Leonard, Joseph, Srinivasan, Gelly, de Brevern, JBSD, 2013). |
