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Resolution and uniqueness of estimated parameters of a model of thin filament regulation in solution

Mijailovich, Srboljub M., Li, Xiaochuan, del Álamo, Juan C., Griffiths, R. Hugh, Kecman, Vokislav, Geeves, Michael A. (2010) Resolution and uniqueness of estimated parameters of a model of thin filament regulation in solution. Computational Biology and Chemistry, 34 (1). pp. 19-33. ISSN 1476-9271. (doi:10.1016/j.compbiolchem.2009.11.002) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:29223)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1016/j.compbiolchem.2009.11.0...

Abstract

The estimation of chemical kinetic rate constants for any non-trivial model is complex due to the nonlinear effects of second order chemical reactions. We developed an algorithm to accomplish this goal based on the Damped Least Squares (DLS) inversion method and then tested the effectiveness of this method on the McKillop–Geeves (MG) model of thin filament regulation. The kinetics of MG model is defined by a set of nonlinear ordinary differential equations (ODEs) that predict the evolution of troponin–tropomyosin–actin and actin–myosin states. The values of the rate constants are estimated by integrating these ODEs numerically and fitting them to a series of stopped-flow pyrene fluorescence transients of myosin-S1 fragment binding to regulated actin in solution. The accuracy and robustness of the estimated rate constants are evaluated for DLS and two other methods, namely quasi-Newton (QN) and simulated annealing (SA). The comparison of these methods revealed that SA provides the best estimates of the model parameters because of its global optimization scheme. However it converges slowly and does quantify the uniqueness of the estimated parameters. On the other hand the QN method converges rapidly but only if the initial guess of the parameters is close to the optimum values, otherwise it diverges. Overall, the DLS method proves to be the most convenient method. It converges fast and was able to provide excellent estimates of kinetic parameters. Furthermore, DLS provides the model resolution matrix, which quantifies the interdependence of model parameters thereby evaluating the uniqueness of their estimated values. This property is essential for estimating of the dependence of the model parameters on experimental conditions (e.g. Ca2+ concentration) when it is assessed from noisy experimental data such as pyrene fluorescence from stopped-flow transients. The advantages of the DLS method observed in this study should be further examined in other physicochemical systems to firmly establish the observed effectiveness of DSL vs. the other parameter estimation methods.

Item Type: Article
DOI/Identification number: 10.1016/j.compbiolchem.2009.11.002
Uncontrolled keywords: Damped Least Squares; Ca2+ sensitivity; Resolution matrix; Tropomyosin–troponin–actin; Stopped-flow
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Susan Davies
Date Deposited: 28 Mar 2012 13:34 UTC
Last Modified: 16 Nov 2021 10:07 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/29223 (The current URI for this page, for reference purposes)

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