title: Exploring the adenylation domain repertoire of nonribosomal peptide synthetases using an ensemble of sequence-search methods.
abstract: The introduction of two-dimension (2D) graphs and their numerical characterization for comparative analyses of DNA/RNA and protein sequences without the need of sequence alignments is an active yet recent research topic in bioinformatics. Here, we used a 2D artificial representation (four-color maps) with a simple numerical characterization through topological indices (TIs) to aid the discovering of remote homologous of Adenylation domains (A-domains) from the Nonribosomal Peptide Synthetases (NRPS) class in the proteome of the cyanobacteria Microcystis aeruginosa. Cyanobacteria are a rich source of structurally diverse oligopeptides that are predominantly synthesized by NPRS. Several A-domains share amino acid identities lower than 20 % being a possible source of remote homologous. Therefore, A-domains cannot be easily retrieved by BLASTp searches using a single template. To cope with the sequence diversity of the A-domains we have combined homology-search methods with an alignment-free tool that uses protein four-color-maps. TI2BioP (Topological Indices to BioPolymers) version 2.0, available at http://ti2biop.sourceforge.net/ allowed the calculation of simple TIs from the protein sequences (four-color maps). Such TIs were used as input predictors for the statistical estimations required to build the alignment-free models. We concluded that the use of graphical/numerical approaches in cooperation with other sequence search methods, like multi-templates BLASTp and profile HMM, can give the most complete exploration of the repertoire of highly diverse protein families.
authors.affiliation: CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Porto, Portugal.
authors.forename: Guillermin
authors.initials: G
authors.lastname: Agüero-Chapin
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Molina-Ruiz
authors.forename: Emanuel
authors.initials: E
authors.lastname: Maldonado
authors.forename: Gustavo
authors.initials: G
authors.lastname: de la Riva
authors.forename: Aminael
authors.initials: A
authors.lastname: Sánchez-Rodríguez
authors.forename: Vitor
authors.initials: V
authors.lastname: Vasconcelos
authors.forename: Agostinho
authors.initials: A
authors.lastname: Antunes
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D010453:Peptide Synthases / Q000737:chemistry*; D017434:Protein Structure, Tertiary
chemical_list: D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase