Pattern databases in protein analysis
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Pattern databases in protein analysis
Arthur Gruber
Instituto de Ciências Biomédicas
Universidade de São Paulo
AG-ICB-USP
Protein databases
• Genpept – protein sequence database translated from GenBank
• UniProtKB/TrEMBL – is a computer-annotated protein sequence database complementing the UniProtKB/Swiss-Prot Protein Knowledgebase.
• UniProtKB/Swiss-Prot – is a curated protein sequence database that provides a high level of annotation, a minimal level of redundancy and a high level of integration with other databases.
AG-ICB-USP
How to assign protein functions? • Similar proteins may share common functions,
but… proteins that share common domains may have evolved to perform distinct functions
• Proteins that exert similar function may share common domains, but… domain sequences are not always very similar – more refined are requires than simply similarity searches
• Proteins may share common domains, but have different architectures – no single domain are necessarily involved with protein function. Many proteins use multiple domains to perform their activities AG-ICB-USP
Some conclusions
• Similarity searches may reveal proteins that share very similar sequences and functions – high similarity over the full length of the query sequence
• An output with no significant hits or with hits to unannotated proteins will no unravel the possible function of the query protein
• Similarity searches do not differentiate orthologues from paralogues
• When matching multidomain proteins, it may not be appropriate to transfer the functional annotation – the context is important!
AG-ICB-USP
Pattern databases
• Databases that contain patterns of residue conservation within groups of related sequences
• There are several methods to determine patterns
• There are many different pattern databases
AG-ICB-USP
Common protein pattern databases
AG-ICB-USP
• Prosite patterns – regular expressions
• Prosite profiles – weight matrices (profiles)
• Pfam – database of protein domain families. Contains curated multiple sequence alignments for each family and corresponding HMMs
• Prints – database of groupf of motifs that in the context of being together, are more potent for assign protein function
• Prodom – automatedly generated databases based on a recursive use of PSI-BLAST similarity searches
• Interpro – an integrated databaes that combines different protein signature recognition methods in one single resource
How to start building a pattern database?
AG-ICB-USP
• Prosite patterns – regular expressions
• Prosite profiles – weight matrices (profiles)
• Pfam – database of protein domain families. Contains curated multiple sequence alignments for each family and corresponding HMMs
• Prints – database of groupf of motifs that in the context of being together, are more potent for assign protein function
• Prodom – automatedly generated databases based on a recursive use of PSI-BLAST similarity searches
• Interpro – an integrated databaes that combines different protein signature recognition methods in one single resource
How to start building a pattern database?
AG-ICB-USP
With multiple sequence alignments of functionally related proteins
Some definitions
AG-ICB-USP
• Protein motif – a single conserved region
• Prosite pattern – a consensus expression of a conserved region
• Frequency matrices (PRINTS) – matrices that contain the frequencies in which residures occur in a given motif
• PSSM – position specific score (weight) matrices (BLOCKS) –add a scoring scheme to the frequency matrices
• HMMs profiles – probabilistic models derived from alignment profiles
• Protein domain - is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain.