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Lecture8 - Lecture 8 Patterns Profiles and Motifs...

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Lecture 8: Patterns, Profiles, and Motifs • Finding patterns in protein and DNA sequences • Calculating profiles of DNA sequences Some slides adapted from slides from Dr. Keith Dunker Some slides adapted from slides created by Dr. Zhiping Weng (Boston University) Definitions and Resources § Motif : A region of a protein or DNA sequence that may be functionally or structurally significant and/or conserved in other sequences • Motifs usually contain biologically important sequences § Pattern : Describes a motif using a qualitative consensus sequence (e.g., IUPAC or regular expression) § Profile : Describes a motif using quantitative information captured in a position specific scoring matrix (weight matrix) § PROSITE is a protein sequence pattern and profile database • http://www.expasy.ch/prosite • Contains >1100 entries describing >1600 patterns and profiles § DNA pattern and profile databases are more fragmented • JASPAR (http://jaspar.genereg.net/ ) and S. cerevisiae Promoter Database (SCPD) (http://rulai.cshl.edu/SCPD/) Importance of Sequence Patterns in Proteins • Conserved patterns in protein sequences usually have important biological functions • Conserved sequence patterns may be indicative of e.g., a protein structural domain, enzyme active site, or a binding site for another protein or metal ion Cu,Zn Superoxide Dismutase Image created using Cn3D from pdb id: 1XSO Steps in the Development of a New PROSITE Pattern (1) Construct a multiple sequence alignment of a protein family (2) Use the alignment to identify conserved or biologically significant residues (e.g., residues in catalytic/active site, binding domain, structural features) (3) Start by creating a core sequence pattern (approximately 4-5 contiguous amino acids in length) (4) Expand the pattern to improve its sensitivity and specificity for detecting known protein family members • Sensitivity : Test the trial pattern against known positive sequences • Specificity : Test the trial pattern against known negative sequences Information from http://ca.expasy.org/prosite/prosuser.html
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Finding Patterns in Multiple Sequence Alignments Baeyer-Villiger monooxygenases (BVMOs) - taken from Fraaije, et al (2002) FEBS Letters 518 :43-47 Pattern of Cu/Zn Superoxide Dismutase § Example of a PROSITE pattern (
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