Fig. 2.

Depiction of the three challenges to advance the modeling and simulation of cellular processes. a In challenge 1, a template space is filled with molecular components of the HIV-1 virus (CellPack image). b In challenge 2, structural simplifications are devised (for a ribosome in this example) to make the relevant timescales accessible to simulations. Subsequently, the functional form of the interactions between any two simplified particles is chosen (single-well potential in this case, black and cyan lines) and the parameters (indicated) on which it depends are calculated. For models including bimolecular reactions, the criteria for each reaction need to be evaluated as well. c In challenge 3, the interactions calculated in challenge 2 are refined by using here, for the specific case of diffusion within the cytoplasm, a reference curve describing diffusive data measured in vivo, over 3 to 4 orders of magnitude in the biomolecule (hydrodynamic) radius. This refinement phase validates the model against experimental cell-scale quantities and produces a more realistic force field compared to the one obtained from challenge 2