This is a mechanistic model of myocardial mitochondrial metabolism including oxidative phosphorylation,
This code reproduces figures from Assessing Potential Mitochondrial Targets in the Failing Heart Using Quantitative Systems Pharmacology
MATLAB
This code was written in Matlab (v. 2019b)
Add all files/directories in this repository to the MATLAB working directory/path.
Run_Final_Figurs.m
-> Script to generate figures from the manuscriptsetup.m
-> Defines constants and initial conditionsdefine_globals.m
-> Defines global variablesCell_dxdt.m
-> Diff Eqs. for cell version of the modelCell_Flux.m
-> Calculates FluxPDHphosdephos.m
-> Calculates phosphorylation status of Pyruvate dehydrogenaseparam14.mat
-> Parameter fileVarstruc_default.mat
-> Variables that change upon pertubations for heart failuree and interventionsRun_substrate_select.m
-> Function to sweep malonyl-coA and PyruvateATP_Hyrdo_Sweep.m
-> Function to increase workrate in mitochodria by increasing ATP hydrolysisGenreate_Fig4b.m
-> Function to reproduce figure 4 of the manuscriptFig6B.m
-> Function to reproduce figur 6B of the manuscript
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setup1.m
-> Defines constants and initial conditions for optimization experiment -
define_global1.m
-> Defines global variables -
define_global_opt.m
- > Defines other global variable options -
IsoMito_dXdT
-> Diff Eqs. for Isolated Mitocondria -
Mito_dXdT.m
-> Diff Eqs. for Mitochondria (similar to IsoMito) for fitting specifity factors in vitro (sf) -
Mito_Flux.m
-> Calculates flux values -
param14.mat
-> Parameter values -
Reproduce_InVitro
-> Function to reproduce in vitro experiments -
InVitroExpCond.m
-> Function to define in vitro experimental conditions -
Run_sf_optimization.m
-> Function to optimize specificity factors in$\beta$ -oxidation enzymes -
Objfun.m
-> Function to define the objective function for the minimization problem -
Plot_variability
-> Plotting functioon - 'dxdt_electrode` -> Function to mimic O2 sensor delay in MVO2 experiments
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Varstruc_default.mat
-> Variables that change upon pertubations for heart failuree and interventions -
s_F.mat
-> Specificity factors -
sf_out.mat
-> Fitted specificity factors -
fluxes.m
-> Calculates flux for VO2 for IsoMito -
Table1.mat
-> Digitized data
To generate figures from the manuscript:
Run_Final_Figures.m
Figures are saved in pdf format
Lyndsey F. Meyer*, Neda Nourabadi, CJ Musante, Daniel A. Beard, Anna Sher
*Correspondence to Lyndsey.Meyer@pfizer.com or Dabeard@med.umich.edu