  Quantitative structure-property relations (QSPR) employing descriptors
derived from the 3D molecular structure are frequently applied for property
prediction in various fields of research. In particular, DragonX is one of the
most widely used software packages for descriptor calculation. The reliability
of 3D molecular descriptors computed by DragonX has lately been investigated,
thereby focusing on the effect of computational methods used for molecular
structure optimization on the accuracy of the resulting molecular descriptors.
The present contribution extends the analysis to a more intrinsic problem of
DragonX descriptor evaluation resulting from the sensitivity of the computed 3D
descriptors on the coordinate system used for molecule description. Evaluating
several 3D descriptors for converged molecular structures rotated around all 3
spatial axes (affine coordinate transformations) yields systematically varying
descriptor values. Since this unphysical behavior severely affects the
descriptor reliability, the present contribution is meant to summarize these
findings for later improvement of either descriptor definitions or the DragonX
implementations.
