Title: RMSD - Routine measure stirs doubts Author: Jeremy Yang OpenEye Abstract: Root mean square distance (RMSD) measurements between molecule conformations are routine and widespread in scientific literature. It appears widely accepted that to measure the difference or sameness between conformers, that is, a distance in "conformation space", a sole RMSD calculation is sufficient. While some interaction models depend on the square of interatomic distance, does this provide a physical basis for use of RMSD? Is the current widespread use of RMSD justified, and if so how? This study examines and evaluates RMSD and its uses, and some alternative measures of distance between conformers.