In this study, computational methods were employed in efforts to elucidate physical mechanisms underlying the ligand selectivity of polymeric sorbents produced through the molecular imprinting of 17-beta-estradiol. Previous computational and experimental studies had identified candidate systems applicable to the development of synthetic polymeric receptors for the detection and possible removal of pollutants with endocrine-disrupting properties. Here we present a series of comprehensive molecular dynamics studies of candidate molecular imprinting prepolymerization systems. The results from the studies highlight the role of the cross-linker and the importance of the interplay between functionalities of the various monomers employed in template complexation. The significance of these results for future studies is discussed.