Physical Properties Based on Sequence

In Chapter 8, the idea of direct sequence comparison was presented, where BLAST searches are performed to identify sequences in the public databases that are similar to a query sequence of interest. Often, this direct comparison may not yield any interesting results or may not yield any results at all. However, there may be very weak sequence determinants that are present that will allow the query sequence to be associated with a family of sequences. By the same token, a family of sequences can be used to identify new, distantly related members of the same protein family an example of this is PSI-BLAST, discussed in Chapter 8. 

The second term requiring definition is pattern or signature. A signature also represents the common characteristics of a protein family (or a multiple sequence alignment) but does not contain any weighting information whatsoever—it simply provides a shorthand notation for what residues can be present at any given position. For example, the signature 

Based on the classic Gribskov method of profile analysis (Gribskov et al., 1987, 

The BLOCKS database utilizes the concept of blocks to identify a family of proteins, rather than relying on the individual sequences themselves (Henikoff and Henikoff, 1996). The idea of a block is derived from the more familiar notion of a motif, which usually refers to a conserved stretch of amino acids that confer a specific function or structure to a protein. When these individual motifs from proteins in the same family are aligned without introducing gaps, the result is a block, with the term block referring to the alignment, not the individual sequences themselves. Obviously, an individual protein can contain one or more blocks, corresponding to each of its fimctional or structural motifs. 

BLOCKS searches can be performed using the BLOCKS Web site at the Fred Hutchinson Cancer Research Center in Seattle. The Web site is straightforward, allowing both sequence-based and keyword-based searches to be performed. If a DNA sequence is used as the input, users can specify which genetic code to use and which strand to search. Regardless of whether the query is performed via a sequence or via keywords, a successful search will return the relevant block. An example is shown in Figme 11.3. In this entry (for a nuclear hormone receptor called a steroid finger). 

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