Integrative structure modeling is a method for using information from multiple sources to compute structural models of biomolecular systems. It proceeds via four steps: (i) defining the model representation, which determines the variables whose values will be computed; (ii) constructing a function for scoring alternative models according to how well they accommodate input information; (iii) searching a space of candidate models for acceptable models; and (iv) analyzing acceptable models to evaluate their fit with input information. These steps are iterated until a model adequate for addressing biological questions is found. In this paper, we draw lessons from integrative modeling about effective integration and about modeling. We describe what it means to integrate information from multiple sources: Integration amounts to distributing information among the four steps of integrative modeling. Theory and data alike can be sources of information; this process thus generates models of information, rather than models of theory or models of data. We then propose heuristics for distributing information and designing multiple iterations of modeling. Effective iteration requires prioritizing the most reliable information and minimizing the time required to obtain an adequate model. Rather than being constructed from theory and assessed using data, models are constructed from any available information and assessed in a coherentist manner.
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