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Improving Sequence Alignments for Intrinsically Disordered Proteins

By Predrag Radivojac, Zoran Obradovic, Celeste J. Brown and A. Keith Dunker


Introduction Amino acid sequence alignment is the cornerstone of bioinformatics. Alignment algorithms include optimal pairwise comparisons, either global or local , as well as heuristic algorithms such as FastA 3 and BLAST . Optimal multiple sequence alignments 5 suffer from exponential complexity with increasing numbers of sequences. Indeed, the multiple alignment problem is NP-complete; furthermore, a scoring system is difficult to define 6 . These facts gave rise to different suboptimal algorithms based on progressive alignments 7, 8 . Finally, there are sequence profiles 9 and hidden Markov models , which exploit position-specific dependencies within protein families. All alignment methods require a scoring system, which is typically adjusted to optimize sensitivity and specificity. In a given twenty-by-twenty scoring matrix, each entry, s ij , is the score when amino acids i and j are aligned opposite one another. Typically, s ij is a function of ) ( )

Year: 2002
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