We devised a strategy, using a de novo building approach, to construct model molecularly imprinted polymers (MIPs) and assess their ability at binding various target molecules. While our models successfully reproduce the gross experimental selectivities for two xanthines, our atomistic models reveal in detail the considerable heterogeneity of the structure and binding mechanisms of different imprints within such a material. We also demonstrate how nonimprinted regions of a MIP are also responsible for much of binding of target molecules. High levels of cross-linking are shown to produce less specific imprints.