As with QR-BH with independent runs, on-the-fly clustered QR-BH generally had a better sampling efficiency than the pure QR method in locating the global minima within each co-crystal/space group system (Table ), as well as in locating low energy structures (Table , S7) on the complex co-crystal energy landscapes. Compared with independent trial QR-BH, the on-the-fly clustering was similarly efficient at sampling the global minima to QR-BH with a fixed, large seed:step ratio (10:1 = 710 seeds × 71 BH steps), because in both cases BH trials are quite short.