To investigate the behaviour of the QR-BH method thoroughly and as a challenge to investigate the efficiency of the method on more complex systems, we applied the algorithm to two co-crystal systems (Fig 2 ), in which the presence of two independent molecules leads to more degrees of freedom and, thus, more challenging energy landscapes for structure prediction. The first cocrystal, which we refer to by the Cambridge Structural Database (CSD) reference code of its known structure, XAFQAZ, is a hydrogen bonded complex between 2,8-Dimethyl-6H,12H-5,11methanodibenzo[b,f] diazocine (Tröger's base) and 3,5dinitrobenzoic acid and was found to be a challenging target in the 6th blind test of crystal structure prediction. As a second co-crystal, we chose the complex between two planar molecules -pyrene and pyromellitic dianhydride -which is held together by weaker, less directional intermolecular interactions. We also ref to this system by the CSD reference code of its known crystal structure,[21] PYRPMA.