title: Prediction of Peptide and Protein Propensity for Amyloid Formation.
abstract: Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔG° values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation.
authors.affiliation: School of Forensic and Investigative Science, University of Central Lancashire, Preston, PR1 2HE, United Kingdom; Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Campus Universitário, Quinta, Da Granja, Monte de Caparica, 2829-511, Caparica, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Família
authors.affiliation: Research and Innovation Office, UCLan Biomedical Research Facility, University of Central Lancashire, Preston, PR1 2HE, United Kingdom; School of Applied Science, London South Bank University, 103 Borough Road, London, SE1 0AA, United Kingdom.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Dennison
authors.affiliation: Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Campus Universitário, Quinta, Da Granja, Monte de Caparica, 2829-511, Caparica, Portugal.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Quintas
authors.affiliation: School of Applied Science, London South Bank University, 103 Borough Road, London, SE1 0AA, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Phoenix
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D058227:Amyloidogenic Proteins / Q000378:metabolism*; D016571:Neural Networks, Computer; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D058227:Amyloidogenic Proteins