title: SnapDRAGON: a method to delineate protein structural domains from sequence data.
abstract: We describe a method to identify protein domain boundaries from sequence information alone based on the assumption that hydrophobic residues cluster together in space. SnapDRAGON is a suite of programs developed to predict domain boundaries based on the consistency observed in a set of alternative ab initio three-dimensional (3D) models generated for a given protein multiple sequence alignment. This is achieved by running a distance geometry-based folding technique in conjunction with a 3D-domain assignment algorithm. The overall accuracy of our method in predicting the number of domains for a non-redundant data set of 414 multiple alignments, representing 185 single and 231 multiple-domain proteins, is 72.4 %. Using domain linker regions observed in the tertiary structures associated with each query alignment as the standard of truth, inter-domain boundary positions are delineated with an accuracy of 63.9 % for proteins comprising continuous domains only, and 35.4 % for proteins with discontinuous domains. Overall, domain boundaries are delineated with an accuracy of 51.8 %. The prediction accuracy values are independent of the pair-wise sequence similarities within each of the alignments. These results demonstrate the capability of our method to delineate domains in protein sequences associated with a wide variety of structural domain organisation.
authors.affiliation: Division of Mathematical Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: George
authors.forename: Jaap
authors.initials: J
authors.lastname: Heringa
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D017421:Sequence Analysis; D012984:Software; D013223:Statistics as Topic
chemical_list: D011506:Proteins