In the framework of our research on the HPLC enantiomeric resolution, several chiral sorbents containing selectors at receptorial level have been prepared and evaluated.In order to have a better understanding of the stereoselective recognition mechanisms at molecular level, we have begun a series of very extensive computations.Enantiodiscrimination systems have been studied according to a general strategy based on a combination of molecular mechanic techniques: conformational searching (systematic, stochastic or molecular dynamic approach), conformational analysis, automatic q uasi flexible docking processing, and final thermodynamic statistical evaluation.In particular, a new procedure (Surface Grid, S -Grid ) has been developed for the systematic search of supra-molecular associates between host receptor and enantiomeric guests; S -Grid is particularly suitable for the simulation of enantioselection processes operated by chiral hosts having clefts or multiple deep cavities on their surfaces.As illustrative examples of the procedure, some simulations (and comparison with experimental data) of the enantioselective interaction between a C3-symmetric macrocycle host and aminoacid derivatives will be shown.In addition, the chiral molecular recognition mechanisms in small bimolecular systems will be investigated; in this contact we focus our attention on the direct resolution of N-(2-naphthyl) alanine methyl ester on (S)-(-)N-(3,5-dinitrobenzoyl) leucine-N-proplylamide chiral stationary phase (CSP).