Abstract
Although chirality-mirror asymmetry-underpins biomolecular interactions, difficulties in quantifying it have long obscured insight into the precise role it plays in these interactions. Two standard chirality measures are the pseudoscalar Osipov-Pickup-Dunmur (OPD) index, which yields an asymmetry index with a sign, and the Hausdorff Chirality Measure (HCM), which yields only a magnitude. Theoretical arguments have shown that OPD is expected to have "chiral zeros," which occur when a chiral object is incorrectly assigned a chirality index value of zero. However, their existence remains theoretical and their abundance in real (bio)molecules has not been studied. We examined the differences between OPD and HCM in four different biological systems representing several different scales of chirality and found chiral zeros to be prevalent in each of these cases. Thus, we conclude that OPD is unsuitable for the quantification of chirality of complex molecular structures except in simple cases of helicoids with singular degrees of freedom for their reconfiguration. HCM also gave a weak correlation with biological properties. Altogether our findings indicate that new mathematical approaches to differentiate opposite handed chiral structures are needed especially considering the rapid prolifiration of machine learning and artificial intelligence algorithms for biochemistry and structural biology.