We assessed the cross-docking performance of AC using the SARS-MP-76 benchmark set and comparing the cross-docking success rates to the re-docking success rates and to the performance of GOLD. We tested different several values of the concavity parameter (N T hr , Figure ) but kept all other sampling parameters fixed (switch method, 90°rotational angle, 8 RIC). A concavity value of 70 gave an insufficient number of attracting points, while 60 and 50 generated enough points to mimic the energetics of the cavity (Figure ). As expected from the assessment of the SARS-MP-76 set (Figure ), re-docking was challenging due to the high solvent exposure and low specificity of the ligands. In fact, only a success rate of 59% was reached in re-docking, compared to 79% for the CSKDE95 and CS244 test sets. A concavity value of 50 gave the best success rates, slightly better than 60 and 70 (Supporting Information, Table ). For cross-docking, a value of 60 gave the best results (success rate of 28%), corresponding to a decrease of 30% from the corresponding re-docking success rate, which is similar to the drop seen in previous cross-docking result of AC. We additionally assessed the influence of a flexible protein environment for cross-docking.