The Gravity Recovery and Interior Laboratory (GRAIL) mission to the Moon utilized an integrated scientific measurement system comprised of flight, ground, mission, and data system elements in order to meet the end-to-end performance required to achieve its scientific objectives. Modeling and simulation efforts were carried out early in the mission that influenced and optimized the design, implementation, and testing of these elements. Because the two prime scientific observables, range between the two spacecraft and range rates between each spacecraft and ground stations, can be affected by the performance of any element of the mission, we treated every element as part of an extended science instrument, a science system. All simulations and modeling took into account the design and configuration of each element to compute the expected performance and error budgets. In the process, scientific requirements were converted to engineering specifications that became the primary drivers for development and testing. Extensive simulations demonstrated that the scientific objectives could in most cases be met with significant margin. Errors are grouped into dynamic or kinematic sources and the largest source of non-gravitational error comes from spacecraft thermal radiation. With all error models included, the baseline solution shows that estimation of the lunar gravity field is robust against both dynamic and kinematic errors and a nominal field of degree 300 or better could be achieved according to the scaled Kaula rule for the Moon. The core signature is more sensitive to modeling errors and can be recovered with a small margin.