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ABSTRACT Simulations of isolated giant molecular clouds (GMCs) are an important tool for studying the dynamics of star formation, but their turbulent initial conditions (ICs) are uncertain. Most simulations have either initialized a velocity field with a prescribed power spectrum on a smooth density field (failing to model the full structure of turbulence) or ‘stirred’ turbulence with periodic boundary conditions (which may not model real GMC boundary conditions). We develop and test a new GMC simulation setup (called turbsphere) that combines advantages of both approaches: we continuously stir an isolated cloud to model the energy cascade from larger scales, and use a static potential to confine the gas. The resulting cloud and surrounding envelope achieve a quasi-equilibrium state with the desired hallmarks of supersonic ISM turbulence (e.g. density PDF and a ∼k−2 velocity power spectrum), whose bulk properties can be tuned as desired. We use the final stirred state as initial conditions for star formation simulations with self-gravity, both with and without continued driving and protostellar jet feedback, respectively. We then disentangle the respective effects of the turbulent cascade, simulation geometry, external driving, and gravity/MHD boundary conditions on the resulting star formation. Without external driving, the new setup obtains results similar to previous simple spherical cloud setups, but external driving can suppress star formation considerably in the new setup. Periodic box simulations with the same dimensions and turbulence parameters form stars significantly slower, highlighting the importance of boundary conditions and the presence or absence of a global collapse mode in the results of star formation calculations.