Introduction to Bioinformatics
This textbook is a solid introduction to the science of Bioinformatics, an integration of computing skills and biological methods.
TABLE OF CONTENTS Introduction to Bioinformatics
Applications of multiple sequence alignments to database searching
Searching in databases for homologues of known proteins is a central theme of bioinformatics. Indeed it brooked no delay; we introduced it in Chapter 1 with the application of PSI-BLAST. We reconsider database searching here, with the goal of trying to understand how we can best use available information to build effective procedures. The goals are high sensitivity - picking up even very distant relationships - and high selectivity - minimizing the number of sequences reported that are not true homologues. Here we discuss how to apply multiple sequences. In Chapter 5 we shall discuss how to apply structural information in addition.
We recognize a familiar face by reacting to its integral appearance rather than to individual features. Similarly, multiple sequence alignments contain subtle patterns that characterize families of proteins.
During the last decade, great progress has been made in devising methods for applying multiple sequence alignments of known proteins to identify related sequences in database searches. The results are central to contemporary applications of bioinformatics, including the interpretion of genomes. Three important methods are: Profiles, PSI-BLAST and Hidden Markov Models (HMMs).
Profiles
Profiles express the patterns inherent in a multiple sequence alignment of a set of homologous sequences. They have several applications:
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They permit greater accuracy in alignments of distantly-related sequences.
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Sets of residues that are highly conserved are likely to be part of the active site, and give clues to function.
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The conservation patterns facilitate identification of other...
Copyright Arthur M. Lesk 2002 under license agreement with Books24x7
