Comparison of sequence and structure alignments for protein domains

Abstract

Profile search methods based on protein domain alignments have proven to be useful tools in comparative sequence analysis. Domain alignments used by currently available search methods have been computed by sequence comparison. With the growth of the protein structure database, however, alignments of many domain pairs have also been computed by structure comparison. Here, we examine the extent to which information from these two sources agrees. We measure agreement with respect to identification of homologous regions in each protein, that is, with respect to the location of domain boundaries. We also measure agreement with respect to identification of homologous residue sites by comparing alignments and assessing the accuracy of the molecular models they predict. We find that domain alignments in publicly available collections based on sequence and structure comparison are largely consistent. However, the homologous regions identified by sequence comparison are often shorter than those identified by 3D structure comparison. In addition, when overall sequence similarity is low alignments from sequence comparison produce less accurate molecular models, suggesting that they less accurately identify homologous sites. These observations suggest that structure comparison results might be used to improve the overall accuracy of domain alignment collections and the performance of profile search methods based on them.

Membrane protein structure quality in molecular dynamics simulation

“…Now that more than one member of these membrane protein families has a solved structure, one could also begin to compare the quality of the homology modeling programs for use with membrane proteins. This has been done for soluble proteins [46]. It could also be used to check the ability of the sequence alignment algorithms for membrane proteins against direct structural alignments-the only truly 'correct' alignment.…”

Comparative and Evolutionary Studies of Vertebrate Extracellular Sulfatase Genes and Proteins: SULF1 and SULF2

“…Predicted secondary structures for the hydrophilic zones for both SULF1 (residues 397-871) and SULF2 (residues 398-870) were undertaken using the PSIPRED web server [35]. Identification of conserved domains for vertebrate SULF1 and SULF2 proteins was made using NCBI web tools [36].…”

CDD: a Conserved Domain Database for protein classification

“…This procedure requires fairly accurate alignments, and frequently we do revise alignment models imported from outside sources. In alignment curation, we consider information from 3D structure and structure superposition, when possible, to define structurally conserved cores, accurately delineate domain boundaries and resolve conflicts between sequence-based alignment methods and structure superposition (5). Alignments curated at the NCBI conform to a simple block-structure, with uniformly aligned, gap-less, structurally conserved blocks separated by unaligned regions, which capture length variation.…”