This paper presents the development of comprehensive computational fluid dynamics models for unsteady flows of coolant through a string of 12 CANDU 6 fuel bundles with angular misalignments inside a pressure tube by means of large eddy simulation. The computational scheme is first validated against the numerical and experimental data available in the literature for an array of parallel rods without end plates. The converged numerical results for the 12-bundle string are then successfully obtained by utilizing 60 supercomputers and parallel processing. The computed mean and root-mean-square values of the lateral fluid forces indicate that it is necessary to model the entire fuel string in a channel to accurately quantify the unsteady flow-induced excitations.