FIGURE 1.

The four stages of integrative modeling. The integrative structure determination procedure proceeds through four stages. First, we collect all information describing the system, including experimental data and physical laws. Second, the representation of the system components is chosen, and each piece of input information is translated into a set of spatial restraints. Third, alternative configurations of the system components are sampled. Fourth, the ensemble of models resulting from sampling are filtered by their fit to the input data, the sampling and model precision computed, and the resulting model ensembles validated against information used and not used in modeling. Should the model not be deemed satisfactory, by either being too imprecise or poorly fit, the process can be iterated, adding more information or increasing sampling, until a satisfactory model is obtained. Steps in the fourth stage covered in this tutorial are outlined with thick lines