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Background  Reproducing cell processes using an in silico system is an essential tool for understanding the underlying mechanisms and emergent properties of this extraordinary complex biological machine. However, computational models are seldom applied in the field of intracellular trafficking. In a cell, numerous molecular interactions occur on the surface or in the interior of membrane-bound compartments that continually change position and undergo dynamic processes of fusion and fission. At present, the available simulation tools are not suitable to develop models that incorporate the dynamic evolution of the cell organelles.    Results  We developed a modeling platform combining Repast (Agent-Based Modeling, ABM) and COPASI (Differential Equations, ODE) that can be used to reproduce complex networks of molecular interactions. These interactions occur in dynamic cell organelles that change position and composition over the course of time. These two modeling strategies are fundamentally different and comprise of complementary capabilities. The ODEs can easily model the networks of molecular interactions, signaling cascades, and complex metabolic reactions. On the other hand, ABM software is especially suited to simulate the movement, interaction, fusion, and fission of dynamic organelles. We used the combined ABM-ODE platform to simulate the transport of soluble and membrane-associated cargoes that move along an endocytic route composed of early, sorting, recycling and late endosomes. We showed that complex processes that strongly depend on transport can be modeled. As an example, the hydrolysis of a GM2-like glycolipid was programmed by adding a trans-Golgi network compartment, lysosomal enzyme trafficking, endosomal acidification, and cholesterol processing to the simulation model.    Conclusions  The model captures the highly dynamic nature of cell compartments that fuse and divide, creating different conditions for each organelle. We expect that this modeling strategy will be useful to understand the logic underlying the organization and function of the endomembrane system.    Reviewers  This article was reviewed by Drs. Rafael Fernández-Chacón, James Faeder, and Thomas Simmen.    Electronic supplementary material  The online version of this article (10.1186/s13062-018-0227-4) contains supplementary material, which is available to authorized users.

Reconstruction of endosomal organization and function by a combination of ODE and agent-based modeling strategies