Steckmann2012 - Amyloid beta-protein fibrillogenesis (kinetics of secondary structure conversion)

View the 2015-10 Model of the Month entry for this model
  public model
Short description
Steckmann2012 - Amyloid beta-protein fibrillogenesis (kinetics of secondary structure conversion)

This model is described in the article:

Steckmann T, Awan Z, Gerstman BS, Chapagain PP.
J. Theor. Biol. 2012 May; 301: 95-102

Abstract:

Amyloid fibrils are a common component in many debilitating human neurological diseases such as Alzheimer's (AD), Parkinson's, and Creutzfeldt-Jakob, and in animal diseases such as BSE. The role of fibrillar ?? proteins in AD has stimulated interest in the kinetics of ?? fibril formation. Kinetic models that include reaction pathways and rate parameters for the various stages of the process can be helpful towards understanding the dynamics on a molecular level. Based upon experimental data, we have developed a mathematical model for the reaction pathways and determined rate parameters for peptide secondary structural conversion and aggregation during the entire fibrillogenesis process from random coil to mature fibrils, including the molecular species that accelerate the conversions. The model and the rate parameters include different molecular structural stages in the nucleation and polymerization processes and the numerical solutions yield graphs of concentrations of different molecular species versus time that are in close agreement with experimental results. The model also allows for the calculation of the time-dependent increase in aggregate size. The calculated results agree well with experimental results, and allow differences in experimental conditions to be included in the calculations. The specific steps of the model and the rate constants that are determined by fitting to experimental data provide insight on the molecular species involved in the fibril formation process.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Kinetics of peptide secondary structure conversion during amyloid β-protein fibrillogenesis.
  • Steckmann T, Awan Z, Gerstman BS, Chapagain PP
  • Journal of theoretical biology , 5/ 2012 , Volume 301 , pages: 95-102
  • Theoretical and Computational Biophysics Group, Department of Physics, Florida International University, Miami, FL 33199, USA.
  • Amyloid fibrils are a common component in many debilitating human neurological diseases such as Alzheimer's (AD), Parkinson's, and Creutzfeldt-Jakob, and in animal diseases such as BSE. The role of fibrillar Αβ proteins in AD has stimulated interest in the kinetics of Αβ fibril formation. Kinetic models that include reaction pathways and rate parameters for the various stages of the process can be helpful towards understanding the dynamics on a molecular level. Based upon experimental data, we have developed a mathematical model for the reaction pathways and determined rate parameters for peptide secondary structural conversion and aggregation during the entire fibrillogenesis process from random coil to mature fibrils, including the molecular species that accelerate the conversions. The model and the rate parameters include different molecular structural stages in the nucleation and polymerization processes and the numerical solutions yield graphs of concentrations of different molecular species versus time that are in close agreement with experimental results. The model also allows for the calculation of the time-dependent increase in aggregate size. The calculated results agree well with experimental results, and allow differences in experimental conditions to be included in the calculations. The specific steps of the model and the rate constants that are determined by fitting to experimental data provide insight on the molecular species involved in the fibril formation process.
Contributors
Audald Lloret i Villas

Metadata information

is
BioModels Database MODEL1407300001
BioModels Database BIOMD0000000533
isDescribedBy
PubMed 22586726
hasTaxon
Taxonomy Homo sapiens
isVersionOf
Gene Ontology inclusion body assembly
Gene Ontology amyloid-beta formation
hasProperty
Human Disease Ontology Alzheimer's disease
Curation status
Curated
  • Model originally submitted by : Audald Lloret i Villas
  • Submitted: Jul 30, 2014 1:33:07 PM
  • Last Modified: Sep 24, 2014 2:16:24 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Sep 24, 2014 2:16:24 PM
    • Submitted by: Audald Lloret i Villas
    • With comment: Current version of Steckmann2012 - Amyloid beta-protein fibrillogenesis (kinetics of secondary structure conversion)
  • Version: 1 public model Download this version
    • Submitted on: Jul 30, 2014 1:33:07 PM
    • Submitted by: Audald Lloret i Villas
    • With comment: Original import of Steckmann2012 - Amyloid beta-protein fibrillogenesis (kinetics of secondary structure conversion)
Curator's comment:
(added: 31 Jul 2014, 11:22:28, updated: 31 Jul 2014, 11:22:28)
Figure 3 of the reference publication has been reproduced here. The mathematical model proposed by the authors fits with experimental data from "Kirkitadze et al., (2001) - Identification and characterization of key kinetic intermediates in amyloid beta-protein fibrillogenesis". The simulation was done using Copasi v4.12 (Build 81) and the plots were generated using Gnuplot. The Copasi file of the model with simulation settings can be downloaded from the below link.