A substitution matrix for structural alphabet based on structural alignment of homologous proteins and its applications

Manoj Tyagi, Venkataraman S. Gowri, Narayanaswamy Srinivasan, Alexandre G. de Brevern, Bernard Offmann
<span title="2006-08-07">2006</span> <i title="Wiley"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/fkowqlvuffe5lnyfwblj3fcp7i" style="color: black;">Proteins: Structure, Function, and Bioinformatics</a> </i> &nbsp;
Analysis of protein structures based on backbone structural patterns known as structural alphabets have been shown to be very useful. Among them, a set of 16 pentapeptide structural motifs known as protein blocks (PBs) has been identified and upon which backbone model of most protein structures can be built. Protein blocks allows simplification of 3D space onto 1D space in the form of sequence of PBs. Here, for the first time, substitution probabilities of PBs in a large number of aligned
more &raquo; ... gous protein structures has been studied and is expressed as a simplified 16x16 substitution matrix. The matrix was validated by benchmarking how well it can align sequences of PBs rather like amino acid alignment to identify structurally equivalent regions in closely or distantly related proteins using dynamic programming approach. The alignment results obtained are very comparable to well established structure comparison methods like DALI and STAMP. Other interesting applications of the matrix have been investigated. We first show that, in variable regions between two superimposed homologous proteins, one can distinguish between local conformational differences and rigid-body displacement of a conserved motif by comparing the PBs and their substitution scores. Second, we demonstrate, with the example of aspartic proteinases, that PBs can be efficiently used to detect the lobe/domain flexibility in the multi-domain proteins. Lastly, using protein kinase as an example, we identify regions of conformational variations and rigid body movements in the enzyme as it is changed to the active state from an inactive state.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1002/prot.21087">doi:10.1002/prot.21087</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/16894618">pmid:16894618</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/fdsjyuez7vdb3j3cmq3332of2u">fatcat:fdsjyuez7vdb3j3cmq3332of2u</a> </span>
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