Coarse-grained chains can be designed so that they successfully capture subtle effects arising from the local covalent structure of real chains. Constraining the conformations of the coarse-grained chains with an appropriate rotational isomeric state model can achieve this objective. This claim has been documented by simulations of the dependence of the mixing behavior of polypropylene melts on the stereochemical composition of the chains; atactic polypropylene and isotactic polypropylene are miscible, but the replacement of either component with syndiotactic polypropylene can lead to immiscibility. This has also been documented by a comparison of simulations and infrared-visible sum frequency generation spectroscopy studies of the surface structures of atactic polystyrene and random copolymers of ethylene and propylene. The success of this method when the stereochemical composition is defined by side chains as small as CH3 suggests that it should also be applicable to other problems in which the influence of the stereochemical composition is less subtle because the stereochemistry is defined by larger side chains. © 2005 Wiley Periodicals, Inc.