Configurational-bias Monte Carlo simulations were carried out on deoxyribonucleic acid (DNA) decamers using a coarse-grained molecular model. The effects of single mutations on the melting transition were investigated as were heterogeneous systems with immobilization of one strand on a surface, both with and without a spacer. The destabilizing effect of an internal mutation is attributed to a lack of cooperativity, which acts through a hydrogen bonding nucleotide's restriction of the conformational freedom of neighboring bases. A surface-oligomer spacer is necessary for duplex stability with the destabilizing effect of the surface coinciding with the volume it excludes. (C) 2009 Elsevier B.V. All rights reserved.