| |
| Constraint-based approaches, such as flux balance analysis (FBA) and energy balance analysis(EBA), are widely applied to study a variety of metabolic networks. While the convex mass-balance solution space has been rigourously characterized, the nonconvex thermodynamically feasible solution space has not been characterized yet, especially for large-scale biochemical networks. Therefore, developing an efficient sampling technique to characterize the physicochemically feasible solution space is critical. Here we present an efficient method to uniformly sample the nonconvex
thermodynamically feasible solution space. By studying the characteristics of sampled flux distributions, the thermodynamic feasibility and directionality of some key reactions are revealed. The developed methodology can be used to revise currently available metabolic networks, and
systematically determine feasible flux directions which satisfy both mass-balance and thermodynamic-balance constraints. |
|
| Keywords:Constraint-based, thermodynamics, nonconvex, sampling, metabolic networks, directionality |
|
