In this study, a docking-based protocol has been probed for its ability to predict the effects of 32 single and double mutations on glycophorin A (GpA) homodimerization. Rigid-body docking simulations have been paralleled by molecular dynamics (MD) simulations in implicit membrane. The rigid-body docking-based approach proved effective in reconstituting the native architecture of the GpA dimer for the wild type and the wild-type-like mutants. The good correlative models between the intermolecular interaction descriptors derived both by rigid-body docking simulations and by MD simulations and experimental relative free energies support the assumption that the mutation-induced changes in the association free energy of GpA helices are essentially ascribed to differences in the packing interactions, whereas almost all the variations in the entropic contributions to the association free energy are constant and/or negligible. The MD-based models achieved provide insights into the structural determinants for disruptive and restoring mutational effects. The computational approaches presented in this study are fast and effective, and constitute simple and promising tools for in silico screening of mutational effects on the association properties of integral membrane proteins.