title: Characterization and prediction of linker sequences of multi-domain proteins by a neural network.
abstract: In this paper, we describe a neural network analysis of sequences connecting two protein domains (domain linkers). The neural network was trained to distinguish between domain linker sequences and non-linker sequences, using a SCOP-defined domain library. The analysis indicated that a significant difference existed between domain linkers and non-linker regions, including intra-domain loop regions. Moreover, the resulting Hinton diagram showed a position-dependent amino acid preference of the domain linker sequences, and implied their non-random nature. We then applied the neural network to predict domain linkers in multi-domain protein sequences. As the result of a Jack-knife test, 58% of the predicted regions matched actual linker regions (specificity), and 36% of the SCOP-derived domain linkers were predicted (sensitivity). This prediction efficiency is superior to simpler methods derived from secondary structure prediction that assume that long loop regions are putative domain linkers. Altogether, these results suggest that domain linkers possess local characteristics different from those of loop regions.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004798:Enzymes / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009415:Nerve Net; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D004798:Enzymes; D011506:Proteins