Protein family search

Wu, C. H., Zhao, S., Chen, H. L Lo, C. J. McLarty, J. (1996). Motif identification neural design for rapid and sensitive protein family search. Comput Appl Biosci 12,109-18. 

Paiacin, M. A new family of proteins (rBAT and 4F2hc) involved in cationic and zwitterionic amino add transport a tale of two proteins in search of a transport function. /. Exp. Biol. 1994, 396, 123-137. 

How does one go about finding all of the relevant proteins in a database once it has been decided to carry out an analysis of an entire protein family The simplest approach is to use similarity search software such as SSEARCH or FASTA (Smith and Waterman, 1981 Pearson and Lipman, 1988) or BLAST (Altschul et al, 1997) with the amino acid sequences of one or two well-known members of the family as queries. The problem is initially the same as that of identifying all proteins that are homologous to a family of proteins, although with some important practical differ-... 

A generic problem with profile methods that iterate is the possibility of profile wander (also called matrix migration). This occurs when sequences found in early rounds of the iterative search are not found in later rounds of the search. This problem affects both PSI-BLAST and HMMER. This means that one should record all the intermediate steps so that these lost members of the family can be recovered. Profile wander only becomes a problem for large protein families, and therefore the cause of the profile wander may be related to the limits of modeling using profiles. 

Correlations in the co-occurrence of domains can assist in the identification of distant members of a protein family that are not detected with significance using standard database searching methods. In all known examples of proteins with Cl and CNH domains, for example, there is an intervening PH domain (Schultz et al., 1998). The only exception to... 

Motif detection involves searching for one sequence within another and is based on the assumption that one sequence is a part of another. Protein motifs are generally short sequences that represent conserved domains (CDs) or characterize protein families. Nucleotide motifs can range in size from full genes within the genome to short enhancer elements. 

Most protein families are characterized by several conserved motifs. The PRINTS hngerprint database was developed to use multiple conserved motifs to build diagnostic signatures of family membership (Attwood et al., 1998). If a query sequence fails to match all the motifs in a given hngerprint, the pattern of matches formed by the remaining motifs allows the user to make a reasonable diagnosis. The PRINTS can be accessed by keyword and sequence searches at http //www.bioinf. 

Against all odds, the pharmaceutical industry began an intensive search for these magic bullets . Fortunately, production and crystallization of kinases is relatively easy in comparison to other protein families, and an impressive number of crystal structures of many kinases and their small-molecule inhibitors has become available (see Figure 7.16, Section 7.4.1). This wealth of structural information has aided the design and synthesis of high-affinity ligands for kinases. An in-depth discussion of these structures is included in Section 7.4. 

Neural network applications for protein sequence analysis are summarized in Table 11.1. Like the DNA coding region recognition problem, signal peptide prediction (11.2) involves both search for content and search for signal tasks. An effective means for protein sequence analysis is reverse database searching to detect functional motifs or sites (11.3) and identify protein families (11.4). Most of the functional motifs are also... 

Henikoff, S. Henikoff, J. G. (1994). Protein family classification based on searching a database of blocks. Genomics 19,97-107. 

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