Cross-docking Cross-docking is a complex computational technique for simultaneously binding several ligands into several target protein configurations ([106]) (Figure ). Therefore, it provides an essential understanding of the selectivity and specificity of interactions between ligands and proteins. For example, it can be helpful to determine off-target binding, which indicates side effects. However, Cross-docking has a disadvantage in that, particularly for large-scale datasets, the considerable processing resources required to dock multiple ligands into several targets concurrently are a burden. Furthermore, cross-docking may have trouble with the precision of scoring systems and the complexity of ligand-protein interactions, which may lead to erroneous positive or negative forecasts of binding affinities. Furthermore, it is limited to applying cross-docking outcomes to different protein families and structural modifications. Thus, careful analysis and result validation are much more critical. Cross-docking remains a valuable technique for examining the interactions between ligands and targets and for spotting new treatment candidates with diverse pharmacological profiles, even if there are challenges ( ).