Sequence information tools

One Holy Grail in protein structure is to develop tools that accurately predict three-dimensional structures of proteins from their primary sequence information [58, 59]. Many of the best tools to date only go part of the way by using known three-dimensional structures from proteins which share similar primary sequence to model the possible structures of new proteins. This technology still has a long way to go, but the potential rewards would be enormous, allowing a genome sequence to be translated into targets for therapeutic intervention in si-lico, in relatively short periods of time. 

Like timelines, sequence diagrams do not identify root causes, and therefore they should be used in conjunction with other tools. The mechanics of these tools are relatively easy to learn, but the investigator must exercise care to avoid locking into a preconceived scenario. For more information on sequence diagram tools refer to Chapter 9. 

The magnitude of the flood of sequence information is a problem - how can it be handled There is also the problem of making sense of the information. Bioinformatics involves the development of tools that can compare vast amounts of sequence data and reduce them to a human scale. 

Putative functional domains within the uncharacterized protein can be identified using the CDD search tools while performing protein-protein BLAST (BLASTP) alignments to obtain insight into possible functions of the predicted protein. The predicted protein sequence is used since amino-acid sequences are more evolutionarily conserved than nucleotide sequences, and therefore a broader search across all available sequence information from a variety of organisms can be conducted to identify potential functionality. Results from the BLASTP and CDD analysis (Fig. 10) have identified... 

It is much easier and quicker to produce sequence information than to determine 3D structures of proteins in atomic detail. As a consequence, there is a protein sequence/structure deficit. In order to benefit from the wealth of sequence information, we must establish, maintain, and disseminate sequence databases provide user-friendly software to access the information, and design analytical tools to visualize and interpret the structural/functional clues associated with these data. 

A number of resources are now available for conducting microbial genome comparisons. Most of these are accessible over the Internet through convenient Web browser interfaces. These resources generally provide sequence information and comparative software as well as computational tools for convenient analysis of the data. 

The progress of peptide research was expedited by the completion of the Human Genome Project. The availability of DNA sequence information has made it possible to rapidly discover new peptides by screening DNA and expression libraries. Using bioinformatic tools (Antelmann et al., 2001 and Chen et al., 2003), numerous as yet unknown putative polypeptides have been predicted as candidates with secretory properties or as proteases. 

The National Center for Biotechnology Information (NCBI). Located at the National Library of Medicine in Bethesda, MD, USA. The home of the GenBank DNA sequence database PubMed literature search engine sequence search tools (e.g., PSI-BLAST) genomic sequence navigation tools. A substantial repository of resources in all areas of bioinformatics. 

A final tool, the use of which will be highlighted in the next chapter, is the computer. Without the computer, it would be impossible to catalog, access, and characterize the abundant information, especially DNA sequence information, that the techniques just outlined are rapidly generating. 

Sequence comparison is a powerful tool for extending our knowledge of protein function and kinship. However, biomolecules generally function as intricate three-dimensional structures rather than as linear polymers. Mutations occur at the level of sequence, but the effects of the mutations are at the level of function, and function is directly related to tertiary structure. Consequently, to gain a deeper understanding of evolutionary relationships between proteins, we must examine three-dimensional structures, especially in conjunction with sequence information. The techniques of structural determination are presented in Chapter 4. 

ESI-MS/MS is another powerful tool for performing tandem mass spectrometry experiments. To get sequence information on the iV-glycan at m/z 2651 (FucHex7HexNAc4 O Fig. 2), the... 

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