Sequence search/alignments

Henikoff, S. (1996). Scores for sequence searches and alignments. Curr. Opin. Struct. Biol. 6, 353-360. 

There are different classes of protein sequence databases. Primary and secondary databases are used to address different aspects of sequence analysis. Composite databases amalgamate a variety of different primary sources to facilitate sequence searching efficiently. The primary structure (amino acid sequence) of a protein is stored in primary databases as linear alphabets that represent the constituent residues. The secondary structure of a protein corresponding to region of local regularity (e.g., a-helices, /1-strands, and turns), which in sequence alignments are often apparent as conserved motifs, is stored in secondary databases as patterns. The tertiary structure of a protein derived from the packing of its secondary structural elements which may form folds and domains is stored in structure databases as sets of atomic coordinates. Some of the most important protein sequence databases are PIR (Protein Information Resource), SWISS-PROT (at EBI and ExPASy), MIPS (Munich Information Center for Protein Sequences), JIPID (Japanese International Protein Sequence Database), and TrEMBL (at EBI). ... 

Yang and Honig have developed the PrISM package of programs that performs structure alignment, PDB sequence search, fold recognition, se-... 

Figure 1.3 shows a partial list of the publicly available SRS servers taking part in the Databank of Databanks project. Each night each SRS Server retrieves information about all the other servers, such as, the databases and applications which that server has. This is then combined to make a searchable database. It is then possible to search for servers which have a particular database (such as all databases which have sequence and align in their description, or the server with the most up to date version of a particular database). 

The TurboWorx Builder software provides prepackaged components for data access, visualization, and algorithms for its target vertical markets including industry-standard sequence analysis utilities for searching, alignment, and HMM algorithms. 

More than 10% of all proteins contain sets of two or more domains that are similar to one another. The afore-described sequence search methods can often detect internally repeated sequences that have been characterized in other proteins. Where repeated units do not correspond to previously identified domains, their presence can be detected by attempting to align a given sequence with itself. 

This may be trivial if sequence identity between the target sequence and a known 3D stmcture is high (say > 30%), as then simple pair-wise sequence comparison methods (FASTA, SSEARCH ) will easily identify the relation-ship. Where sequence identity is lower and a superfamily or even fold relationship must be identified, recognition of the stmctural similarity between two sequences may be very difficult. Sequence-only methods, such as PSI-BLAST, hidden Markov models and intermediate sequence search, use information from multiple sequence alignments to represent the characteristics shared by related sequences (sequence profiles), and use this to search for stmctural homologues. These profiles can then be augmented by secondary stmcture prediction. ... 

Find the sequences to align by database searching or by other means. 

Ideally, assess the similarities within the set of sequences by comparing them pairwise with randomizations. Select a subset of the sequences to align first that cluster above 6cr. Automatic aligmnent of such sequences are likely to be accurate (Barton and Sternberg, 1987). An alternative to doing randomization is to align only sequences that are similar to the query in a database search, say with an E-value of <1. 

There are two basic search strategies for finding a set of related sequences, namely keywords and similarity. A keyword search identifies sequences by looking through their written descriptions (i.e. the annotation section of a database file) and a similarity search looks at the sequences themselves. The keyword search is easier and seems more intuitive, but it is far from exhaustive. The main search engines for similarity search/ alignment are Entrez (NCBI) at http //www.ncbi.nhn.nih.gov/Entrez/ and SRS at http //srs.ebi.ac.uk/... 

Figure 10.3 Sequence information captured from the PDB illustrated for PDB complex 5hvp, HIV protease with acetyl-pepstatin. (a) The raw sequence can be used by standard sequence searching and matching tools, for example, BLAST, (b) The distance annotation permits any sequence information, for example, alignment to be focused down to the binding site sequence as defined by residues within 2,4,6, or 8 Aofthe calculated cavity, (c) PDB 3D coordinate file...

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