AlignmentBasics

AlignmentBasics - Alignment basics Why do we need...

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Unformatted text preview: Alignment basics Why do we need alignment? • To predict function of proteins or RNAs – Complication: function evolves! • To predict structure of proteins or RNAs – a.k.a. “Homology Modelling” – General (“X and Y have the same fold”) – Specific (comparative modeling) • To identify conserved elements – critical residues in proteins (active sites, binding pockets) – functional domains in proteins – protein-coding genes in genomes (“Comparative genomics”) • To study molecular evolution In essence, “alignment” is the basic operation of comparing sequences to see if & how they are related Function Prediction Function Prediction • Function prediction by homology – a gene or protein is compared against other genes or proteins in a database – if a sequence can be detected whose similarity is statistically significant, the function of the unknown gene or protein is inferred. – first-order approximation of the molecular function of the proteins encoded in a genome – prioritize experimental investigation Inference of function Example: p53 tumor suppressor. Inactivated (sequestered by) mdm2; activated by DNA damage Many experiments in mice, fruitflies, yeast (e.g. response to DNA damage first demonstrated using mouse homologue TP53; cell cycle mostly figured out in yeast) Many other examples of homology models (e.g. fruitfly limb development) Complications Complications • Many proteins belong to large families . – Composed of subfamilies by gene duplication events • Gene duplication allows one copy to assume a new biological role through mutation – Hence, subfamilies often differ in their biological functionality yet still exhibit a high degree of sequence similarity. • Other complications – Ignoring the multi-domain organization of proteins. – Error propagation – Insufficient masking of low complexity regions – Alternative splicing – Recombination, “gene conversion” Why Do We Need Homology Modeling?...
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This note was uploaded on 12/03/2011 for the course BIO 118 taught by Professor Staff during the Fall '08 term at Rutgers.

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AlignmentBasics - Alignment basics Why do we need...

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