Sequence motifs/patterns

In order to check whether the occurrence of the Rieske-type sequence motif is unique for the assimilatory nitrite reductase from Bacillus subtilis, the sequences of other assimilatory nitrite reductases were searched for the presence of the four putative ligands of Rieske-type clusters. A well-conserved sequence pattern... 

Noteworthy in this perspective is the recent work done at Pfizer and Biofocus (see Section 5.5), where, based on analysis of sequence data, mutation data, and physicochemical properties of the ligands, approaches were outlined for discovering sequence patterns characteristic of specific ligand classes. Pfizer applied the approach successfully to the construction of a sequence motif characteristic of monoamine GPCRs [74],... 

From the analyses of many glycosylation sites (GalNAc transferase acceptor sites), a few rules of thumb have been formulated (Wilson et al., 1991) and motif patterns have been proposed (Pisano et al., 1993). Matrix statistics have been compiled for site prediction (Elhammer et al., 1993). However, since there is no clear consensus acceptor sequence pattern and it is strongly influenced by the local conformation, neural network is appropriate for the task. 

There are other approaches to family databases that rely more extensively on sequence similarity to define classes of genes or proteins. For example, PROSITE (49) is a resource that uses regular expressions to define patterns of residues that represent biologically significant sequence motifs. Recent versions have incorporated profiles, weight matrices that express the characteristics of a gene... 

A third approach, pioneered by the group of Liebler [19, 34], involves a pattern recognition software called scoring algorithm for spectral analysis (SALSA) to search specific sequence motifs in the MS-MS data. Potential applications envisaged for SALSA include identification of specific protein modifications, e.g., PTM, identifications of peptides with common sequences, e.g., wild-type and mutant forms, and targeted analysis of isoforms and conformers in complex samples. 

The PROSITE database" " of protein sequence motifs is a standard. The motifs are represented by patterns and profiles. Patterns are denoted using the single letter amino acid alphabet, with each position separated by a hyphen, e.g., A-D-E. X is used if any residue is allowed. If several residues are allowed at a given position, they are grouped in square brackets (e.g., [AC]-D-E). Disallowed residues are grouped in curly brackets A-D- FGH. A repeat is indicated by its length after the... 

Recursive dynamic programming (RDP) Another heuristic search procedure based on a branch-and-bound approach has been described in [188]. The approach tries to avoid the restrictions implied by a predefined structural core. Even if the structural core is correctly and completely defined, even the best alignment of the query sequence onto the structure core can be based on information of about half or less of the residues and structural positions of the template structure. Often, structures contain highly conserved loop regions, which if responsible for conserved functions (e.g. ATP binding loops [170]) are also conserved on the sequence level or contain detectable sequence motifs or functional patterns. Such loops can provide important initial hints on similarities and partial alignments exploitable for the assembly of overall alignments. 

In addition to conventional sequence motifs (Prosite, BLOCKS, PRINTS, etc.), the compilation of structural motifs indicative of specific functions from known structures has been proposed [268]. This should improve even the results obtained with multiple (one-dimensional sequence) patterns exploited in the BLOCKS and PRINTS databases. Recently, the use of models to define approximate structural motifs (sometimes called fuzzy functional forms, FFFs [269]) has been put forward to construct a library of such motifs enhancing the range of applicability of motif searches at the price of reduced sensitivity and specificity. Such approaches are supported by the fact that, often, active sites of proteins necessary for specific functions are much more conserved than the overall protein structure (e.g. bacterial and eukaryotic serine proteases), such that an inexact model could have a partly accurately conserved part responsible for function. As the structural genomics projects produce a more and more comprehensive picture of the structure space with representatives for all major protein folds and with the improved homology search methods linking the related sequences and structures to such representatives, comprehensive libraries of highly discriminative structural motifs are envisionable. 

Key Words Motif discovery sequence motif sequence pattern protein domain multiple alignment position-specific scoring matrix PSSM position-specific weight matrix PWM transcription factor-binding site transcription factor promoter protein features. 

Biological sequence motifs are short, usually fixed-length, sequence patterns. Many features of DNA, RNA, and protein molecules can be well approximated by motifs. For example, sequence motifs can represent transcription factor... 

The typical analysis, which is described in this protocol, consists in using successively different tools to go from a list of genes to a graphical map showing the instances of the significant motifs (sequence retrieval -> pattern discovery -> pattern matching -> feature-map). For this purpose, the tools are interconnected the result of one tool can be sent as input for the next tool (piping). 

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