ROSHAMBO overcomes all three of the above challenges, and offers users the ability to run 3D molecular alignment and similarity scoring with industrially-enabling performance and accuracy, completely in the open source. It calculates Tanimoto and Tversky scores for both shape and color, and these scores compare favorably to another open-source tool. We are actively developing a ROSHAMBO optimizer that incorporates both shape and color; in practice, however, shape optimization alone is sufficient to generate near state-of-the-art chemical alignments, and calculation of both color and shape scores post-optimization allows a user to ensure the top hits match the query both in overall shape and in key chemotypes.