Analysis of enzyme kinetic data for mtDNA replication.
A significant amount of experimental data on the reaction kinetics for the mitochondrial DNA polymerase gamma exist, but interpreting that data is difficult due to the complex nature of the function of the polymerase. In order to model how these measured kinetics values for polymerase gamma affect the final function of the polymerase, the replication of an entire strand of mitochondrial DNA, we implement a stochastic simulation of the series of reaction events that the polymerase carries out. These reactions include the correct and incorrect polymerization events, exonuclease events which may remove both incorrectly and correctly matched base pairs, and the disassociation of the polymerase from the mitochondrial DNA template. We also describe other reactions which may be included, such as the addition of nucleoside analog tri-phosphates as substrates. The simulation analysis of the kinetics data is implemented through a standard Gillespie algorithm. We describe the methods necessary to define, code and test this algorithm, as well as describing the hardware and software options that are available.
Song
Zhuo
Z
Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Samuels
David C
DC
D000465:Algorithms; D000074002:DNA Polymerase gamma; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000096:biosynthesis* / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D009154:Mutation; D013269:Stochastic Processes; D013379:Substrate Specificity
D004272:DNA, Mitochondrial; D003854:Deoxyribonucleotides; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase