title: PAT: predictor for structured units and its application for the optimization of target molecules for the generation of synthetic antibodies.
abstract: BACKGROUND
  The identification of structured units in a protein sequence is an important first step for most biochemical studies. Importantly for this study, the identification of stable structured region is a crucial first step to generate novel synthetic antibodies. While many approaches to find domains or predict structured regions exist, important limitations remain, such as the optimization of domain boundaries and the lack of identification of non-domain structured units. Moreover, no integrated tool exists to find and optimize structural domains within protein sequences.
  
  
  RESULTS
  Here, we describe a new tool, PAT ( http://www.kimlab.org/software/pat ) that can efficiently identify both domains (with optimized boundaries) and non-domain putative structured units. PAT automatically analyzes various structural properties, evaluates the folding stability, and reports possible structural domains in a given protein sequence. For reliability evaluation of PAT, we applied PAT to identify antibody target molecules based on the notion that soluble and well-defined protein secondary and tertiary structures are appropriate target molecules for synthetic antibodies.
  
  
  CONCLUSIONS
  PAT is an efficient and sensitive tool to identify structured units. A performance analysis shows that PAT can characterize structurally well-defined regions in a given sequence and outperforms other efforts to define reliable boundaries of domains. Specially, PAT successfully identifies experimentally confirmed target molecules for antibody generation. PAT also offers the pre-calculated results of 20,210 human proteins to accelerate common queries. PAT can therefore help to investigate large-scale structured domains and improve the success rate for synthetic antibody generation.
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, M5S 3E1, ON, Canada.
authors.forename: Jouhyun
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, M5S 3E1, ON, Canada.
authors.forename: Roland
authors.initials: R
authors.lastname: Arnold
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, M5S 3E1, ON, Canada.
authors.forename: Fateh
authors.initials: F
authors.lastname: Singh
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, M5S 3E1, ON, Canada.
authors.forename: Joan
authors.initials: J
authors.lastname: Teyra
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, M5S 3E1, ON, Canada.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Braun
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, M5S 3E1, ON, Canada. pi@kimlab.org.|Department of Molecular Genetics, University of Toronto, Toronto, M5S 3E1, ON, Canada. pi@kimlab.org.|Department of Computer Science, University of Toronto, Toronto, M5S 3E1, ON, Canada. pi@kimlab.org.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D019540:Area Under Curve; D030562:Databases, Protein; D006801:Humans; D020407:Internet; D019151:Peptide Library; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000276:immunology; D012372:ROC Curve; D014584:User-Computer Interface
chemical_list: D000906:Antibodies; D019151:Peptide Library; D011506:Proteins
keywords: Antibody target molecules; Phage display; Protein domain; Protein sequence; Putative structural unit; Structural domains; Synthetic antibody