I wouldn't be too sure about that. One would have to calculate:
1. Velocity and mass of the vessel.
Just like any sim
2. Amount of gravity produced by celestial body in which the vessel orbits.
One single vector, just like any other sim.
3. The amount of gravity produced by the sun.
Another vector, exactely the same principle as the planet you are orbiting around, no differences at all.
4. The amount of gravity produced by other celestial bodies and their influence on other bodies.
Same as the sun, one vector each.
5. Gravitational anomalies.
agree on this one, but I would like to know which sims are currently handling that ? Very few I think, no even Orbiter.
6. The amount of mass in which the vessel loses over time as its fuel is expended.
Just modifing one single variable.
You can imagine the math from here on out. Why do you think only the best and brightest can work in NASA?

Those maths are exactely the same as those used for atmosphere flying. This is simply movement equations. Remember your physics lessons at school ?
Now the thing is, when you are in the atmosphere, you have everything you have in space, and ADDITIONNALY, you have the effects of the atmosphere on the movements of your plane: drag, effects of control surfaces, effect on engine thrust etc...
Atmosphere flying is MUCH more complex than space flying. When you are in the atmosphere, you are into space...but there is additionnaly some gaz all around you, so you have to compute the additionnal effects.