After assessing the reliability of the QR-BH method on the relatively simple single-component molecular crystal systems, the question arose naturally how the parameters of QR-BH would affect the sampling efficiency and whether there is an optimal parameter set to maximize efficiency. To test the influence of QR-BH parameters, we applied the method to the more challenging co-crystal systems, one being a hydrogen bonded co-crystal (XAFQAZ, Fig. ) and the other held together by weaker, less directional interactions (PYRPMA, Fig. ). PYRPMA was explored in three common space groups (P 1, P 2 1 and P 2 1 /c), which includes the space group in which the known crystal structure is found (P 2 1 ). The known crystal structure of XAFQAZ is found in space group P 2 1 /c and we also investigated F 2dd Table : Steps required to locate the global energy minimum and experimental structures for TTBI in 7 space groups. The target structures are listed in order of increasing energy from left to right. QR-BH results are the mean over three repeats of the search, each starting from the same QR seed structures. Results for space group F 2dd and I4 1 /a are not shown because none of the experimentally observed structures, nor the overall global minimum structure, can be located in these space groups. and I4 1 /a for this co-crystal. These space groups were chosen so that, across the two co-crystal systems, we explored different types of intermolecular interactions and a range of crystal symmetries. The perturbation cut-offs for Monte Carlo moves during basin hopping simulations were kept the same as those used for TTBI and both temperatures (500 K and 3000 K) were evaluated. The introduction of a second molecule in the asymmetric unit increases the dimensionality of configurational space by 6 (compared to single component crystals), so we increased length of searches to thoroughly explore the more complex crystal energy landscapes. Pure QR searches were run for a total of 50,000 minimizations and QR-BH were run with just over 50,000 total minimizations. Because of the greater complexity of their search space, we used the co-crystal systems to explore the impact of changing the allocation between QR seeds and BH steps, keeping a fixed total computational budget. Three seed:step ratios were applied: 1:1 (225 seeds × 225 BH steps), 2:1 (316 seeds × 158 BH steps) and 10:1 (710 seeds × 71 BH steps). The higher ratios test the effectiveness of shorter basin hopping trajectories started from a larger set of QR seed structures, which has the advantage of greater parallelizability.