They design it so that once started it will run with no interference from either of them or anyone else until it is done.

This is the case of the "dream-maker on full autopilot", right?

But I'm curious about Bob. Can Bob meddle with the simulation if he decides he wants to? Can he hit the off switch? Cut the wires? Smash the computing substrate into tiny little pieces?

To the extent that this sim has gods, Alice is one.

Why so? Alice is not a god. She has no special ("supernatural") powers. Since we are talking about our empirical reality maybe/possibly being a simulation, Alice even does not remember being outside of the simulation. She is just another unique snowflake in the Matrix. Now, Bob, he's in a very different position.