title: NRPSpredictor2--a web server for predicting NRPS adenylation domain specificity.
abstract: The products of many bacterial non-ribosomal peptide synthetases (NRPS) are highly important secondary metabolites, including vancomycin and other antibiotics. The ability to predict substrate specificity of newly detected NRPS Adenylation (A-) domains by genome sequencing efforts is of great importance to identify and annotate new gene clusters that produce secondary metabolites. Prediction of A-domain specificity based on the sequence alone can be achieved through sequence signatures or, more accurately, through machine learning methods. We present an improved predictor, based on previous work (NRPSpredictor), that predicts A-domain specificity using Support Vector Machines on four hierarchical levels, ranging from gross physicochemical properties of an A-domain's substrates down to single amino acid substrates. The three more general levels are predicted with an F-measure better than 0.89 and the most detailed level with an average F-measure of 0.80. We also modeled the applicability domain of our predictor to estimate for new A-domains whether they lie in the applicability domain. Finally, since there are also NRPS that play an important role in natural products chemistry of fungi, such as peptaibols and cephalosporins, we added a predictor for fungal A-domains, which predicts gross physicochemical properties with an F-measure of 0.84. The service is available at http://nrps.informatik.uni-tuebingen.de/.
authors.affiliation: Applied Bioinformatics, Center for Bioinformatics, Department of Computer Science, University of Tübingen, Sand 14, 72076 Tübingen, Germany. roettig@informatik.uni-tuebingen.de
authors.forename: Marc
authors.initials: M
authors.lastname: Röttig
authors.forename: Marnix H
authors.initials: MH
authors.lastname: Medema
authors.forename: Kai
authors.initials: K
authors.lastname: Blin
authors.forename: Tilmann
authors.initials: T
authors.lastname: Weber
authors.forename: Christian
authors.initials: C
authors.lastname: Rausch
authors.forename: Oliver
authors.initials: O
authors.lastname: Kohlbacher
mesh_terms: D001185:Artificial Intelligence; D020134:Catalytic Domain; D020407:Internet; D010453:Peptide Synthases / Q000737:chemistry*; D012984:Software; D013379:Substrate Specificity
chemical_list: D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase