ROCS was run with factory settings with the following exceptions: both "-besthits" and "maxhits" were set to "0" in order to cause ROCS to retain all results. The "-rankby" option was set to an appropriate value in order to have the results ranked by the four similarity metrics. For experiments using ShapeTanimoto score, the "-shapeonly" function was enabled in order to cause ROCS to align molecules by taking only molecular shape into account (and not color).