TY - GEN A1 - Müller, Arne C. A1 - Bockmayr, Alexander T1 - Fast Thermodynamically Constrained Flux Variability Analysis N2 - Flux variability analysis (FVA) is an important tool to further analyze the results obtained by flux balance analysis (FBA) on genome-scale metabolic networks. Standard FVA may predict unbounded fluxes through some reactions in the network even if the nutrient uptake rate is bounded. These fluxes violate the second law of thermodynamics. They may be eliminated by extending flux variability analysis with thermodynamic constraints. We present a new algorithm for efficient flux variability (and flux balance) analysis with thermodynamic constraints, suitable for analyzing genome-scale metabolic networks. We first show that flux balance analysis with thermodynamic constraints is NP-hard. Then we derive a theoretical tractability result, which can be applied to metabolic networks in practice. We use this result to develop a new constraint programming algorithm Fast-tFVA for fast flux variability analysis with thermodynamic constraints (tFVA). Computational comparisons with previous methods demonstrate the efficiency of the new method. For tFVA, a speed-up of factor 30-300 is achieved. In an analysis of genome-scale metabolic networks in the BioModels database, we found that in 485 out of 716 networks additional irreversible or fixed reactions could be detected. KW - Constraint-based modeling, metabolic network, thermodynamic constraints Y1 - 2012 UR - https://opus4.kobv.de/opus4-matheon/frontdoor/index/index/docId/1187 UR - https://nbn-resolving.org/urn:nbn:de:0296-matheon-11874 ER -