Conformational analysis of heparin epoxide: molecular mechanics computations

The conformation of models of the epoxy-derivative of the glycosaminoglycan heparin has been studied by molecular mechanics calculations using a MM2-like force field extended with parameters for the oxirane ring. Two dimers, two trimers and several higher homologs modeling heparin epoxide were investigated, assuming the preferred 5H0 ring form of 2,3-anhydro-α-l-guluronic acid residue. Two-dimensional (ϕ; ψ) maps of dimers showed the location of the energetically preferred conformers. Starting from the most stable dimer conformers, structures of trimers and other oligomers were derived and optimized, with an exhaustive search of the preferred sidechain conformers. The effect of solvation on conformation was analyzed using a continuum model of solvent. The present calculations indicate a significant flexibility of the heparin epoxide chain.