Computational studies in enantioselective liquid chromatography: Forty years of evolution in docking- and molecular dynamics-based simulations

A key issue in enantioselective analysis is the determination of the enantiomeric elution order. To this aim, many computational modeling studies have been published in the last four decades. Docking and molecular dynamics simulations often supported by quantum mechanical and/or experimental spectroscopic and crystallographic analyses have been applied to gain a deeper insight into the main forces driving the enantiorecognition mechanism and, in turn, the enantiomer elution order. Very interestingly, almost all the relevant materials for enantioselective chromatography applications have been modeled over the years, spanning from high- to low-molecular weight chiral selectors together with the most relevant elution modes. In this review, examples from literature are presented to highlight the main improvements made in terms of accuracy, methodologies and computational performance. As concluding remarks, a critical evaluation of strength points and limitations of the treated in silico methods is discussed.