Question-and-Answer Resource for the Building Energy Modeling Community
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In OpenStudio, you can combine multiple spaces (modeled as individual volumes, with their own internal load values) that have similar temperature setpoints and HVAC equipment into a single thermal zone. If the spaces have adjacent surfaces, OpenStudio will translate those surfaces to Internal Mass objects in EnergyPlus, calculated from the surface constructions.
The impact of doors would likely depend on the size of the building and number of doors. I've typically neglected them for large whole-building models. I imagine they add to simulation time as any additional surface would.
Some more information on reducing run-time can be found in the 'Tips and Tricks' document, as well as research papers and this Unmet Hours question.
