If you were to build a simulation of the universe on a computer, any intelligent life that would eventually rise would, I assume, act and 'think' just as we do, with increasing amounts of processing power as their brains allow them. They would search for answers to the origin of the universe but in a simulation I would assume they would observe mathematical constants and phenomena stemming from undetectable origins.
In short, would a simulated civilization of life ever be able to discover that they are indeed just a computer simulation? I say it is likely not possible, though I also think that such a simulated universe's inhabitants would be just as real as we ourselves are, in terms of their experiences and beliefs.
I don't personally believe we are living in a simulation, but I don't discount the possibility of anything I don't know the absolute truth about.