Introducing thermodynamics into ME-models and crowders into kinetic models

The field of COBRA has impressively evolved since the first meeting in Iceland 7 years ago. The recent trends are moving towards the introduction of constraints that capture mRNA and protein expression (ME-models), thermodynamics and metabolomics (TFA), and most recently kinetics. While these additional constraints expand the capabilities and the scope of the models, they also introduce computational and modeling challenges. We will discuss here these challenges and we will present some new and computationally efficient problem formulations that allow the introduction of thermodynamic constraints into ME-models, and they also consider the effect of intracellular crowding conditions.