you can get 95% of the effects of macromolecular crowding by just shoving PEG into the system (the very first paper we covered in grad school showed that proteins in packed cells have elevated kinetic rates and free enegry of ATP hydrolysis isn't the value measured at STP, by using PEG as a proxy).

If I were to attempt to do gene regulation studies by MD (I share your skepticism!) I would just put a bunch of PEG in as a water replacement.

In fact that's a paper right there- "Effect of increasing macromolecular crowding on the accuracy of DNA simulations for regulation prediction" :)