Reaction kinetics of catalyzed competitive heteropolymer cleavage

S. Kashif Sadiq, Balázs Könnyü, V. Müller, Peter V. Coveney

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A theoretical formulation for complete heteropolymer degradation is developed in terms of Michaelis-Menten reaction kinetics under the quasi-steady-state approximation. This allows the concentration of the entire intermediate decomposition cascade to be accounted for as well as each species of emerging final product. The formulation is implemented computationally and results in stable reaction kinetics across a range of orders of magnitude for KM and kcat. The model is compared with experiment, specifically in vitro HIV-1 protease-catalyzed retroviral Gag-polyprotein processing. Using an experimentally determined cleavage-polypeptide parameter set, good qualitative agreement is reached with Gag degradation kinetics, given the difference in experimental conditions. A parameter search within 1 order of magnitude of variation of the experimental set results in the determination of an optimal parameter set in complete agreement with experiment which allows the time evolution of each individual as well as intermediate species in Gag to be accurately followed. Future investigations that determine the required enzymatic parameters to populate such a scheme will allow for the model to be refined in order to track the time for viral maturation and infectivity.

Original languageEnglish
Pages (from-to)11017-11027
Number of pages11
JournalJournal of Physical Chemistry B
Volume115
Issue number37
DOIs
Publication statusPublished - Sep 22 2011

Fingerprint

Reaction kinetics
cleavage
reaction kinetics
gag Gene Products
Degradation
Polypeptides
Experiments
degradation
Decomposition
formulations
Peptides
protease
human immunodeficiency virus
Kinetics
quasi-steady states
polypeptides
Processing
emerging
cascades
decomposition

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Reaction kinetics of catalyzed competitive heteropolymer cleavage. / Sadiq, S. Kashif; Könnyü, Balázs; Müller, V.; Coveney, Peter V.

In: Journal of Physical Chemistry B, Vol. 115, No. 37, 22.09.2011, p. 11017-11027.

Research output: Contribution to journalArticle

Sadiq, S. Kashif ; Könnyü, Balázs ; Müller, V. ; Coveney, Peter V. / Reaction kinetics of catalyzed competitive heteropolymer cleavage. In: Journal of Physical Chemistry B. 2011 ; Vol. 115, No. 37. pp. 11017-11027.
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