Computational characterization of flexible and polar carbohydrates poses a challenge to current methodologies. We explore a reparametrized semi-empirical quantum mechanical approach within the framework of the PM3 model. Based on fitting to 1,2-ethanediol structures and energies, the modified PM3 Hamiltonian, denoted PM3CARB-1, exhibits improved performance in a number of respects. In particular, C-1(4) ring conformers of glucopyranose are now correctly predicted to be higher in energy than C-4(1) structures. Hybrid quantum mechanical/molecular mechanical molecular dynamics simulations of a model disaccharide, using this PM3CARB-1 model, do not exhibit transitions from C-4(1) to C-1(4) structures. (C) 2004 Elsevier B.V. All rights reserved.