A simplified computational model was proposed to simulate the synthesis of molecularly imprinted polymers (MIP), removal of template and recognition of the template and its analogues by MIP. The MIPs with nicotinamide and iso-nicotinamide as templates were prepared using methacrylic acid as functional monomer. Based on our computational model, the interaction energies between the monomer and the template or its analogues were calculated, which were well correlated with the retention factors and imprinting factors obtained on HPLC columns packed with the corresponding MIP particles. The imprinting effects of the template and its analogues were also investigated from the viewpoint of conformational analysis. The computational data were successfully used to predict the chromatographic behaviour of some chemicals in separation on HPLC columns. We believe that the computational method will find application in designing monomers for MIP synthesis and in studying recognition of templates and their analogues on MIP.