Homology search

Building sequence profiles or Hidden Markov Models to perform more sensitive homology searches. A sequence profile contains information about the variability of every sequence position, improving structure prediction methods (secondary structure prediction). Sequence profile searches have become readily available through the introduction of PsiBLAST [4]... 

However, this is not so easy without the tertiary structure of the enzyme. The possible clues are the homology search with functionally resembling enzymes and computer simulation of the tert-structure of the enzyme. The characteristic features of AMDase are (i) the reaction proceeds via an enolate-type transition state, (ii) the cysteine residue plays an essential role and (iii) the reaction involves an inversion of configuration on the a-carbon of the carboxyl group. 

The identification of the fold is, however, only a minor part of protein characterization. Function is a loosely defined term, but must be viewed within a particular context, e.g., protein function can only take place with an interaction partner or within cellular cascades and networks. Fold predictions and homology searches can only give partial answers to such higher order functions. Thus, independent functional features have to be collected and put into context. Such features include not only molecular properties, but also cellular roles, expression patterns, dysfunctions, pathway context, and subcellular localization. The latter can be predicted by exploiting a variety of methods and localization sites. Kenta Nakai reviews many such sites and their implementation... 

Loros Certainly, but if you get rid of the PAS domains in White Collar 1, BMALl is still going to come up in a sequence-based homology search like BLAST. 

If PMF and sequence homology searches fail using available protein and EST databases, mass spectrum data can, in principle, be used to search genome databases (GenBank http //www.ncbi.nlm.nih.gov/). However, only a small percentage of large genomic sequences code for proteins such that bioinformatics still needs to accurately define exon-intron structures (Andersen and Mann, 2000). 

The regions flanking acyA were sequenced. Several genes involved in carbomycin biosynthesis have been identified after sequence homology searches or expression experiments (Ref. 20 and A. Arisawa, unpublished data, 1999). The carbomycin biosynthetic genes identified by us and/or the Eli Lilly research group so far are summarized in Fig. 5. 

Candidate genes can be selected using a variety of approaches such as literature searches, genes resulting from experiments in animal models, homology searches, and gene expression experiments. Studies testing even dozens of candidates at once exist for many complex diseases cardiovascular disease (83), osteoarthritis (84), and asthma (85) to name a few. 

Submit the following nucleotide sequence to homology search with the BLAST tool at one of the three major nucleotide sequence databases. 

Similarity search can be performed with the FASTA program, though BLAST is easier to use. Both FASTA and BLAST homology searches are also available at EBI, PIR and DDBJ. The small P values indicate homologous sequences. 

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