Molecular Modeling Studies on Unbranched Complex Carbohydrates

Abstract

A general molecular modeling methodology particularly suitable for unbranched complex carbohydrates was described. This methodology employed molecular dynamics (MD) and energy minimization (EM) procedures together with inter-residue spatial constraints across the linkages derived from 2D-NOESY spectroscopy. The first step in this methodology is the generation of a wide variety of starting conformations that span the (φ,ψ) space for each linkage. In the present study, for each linkage, nine starting conformations that span the (φ,ψ) space in a resonable manner were constructed using the torsion angles φ and ψ corresponding to the gauche+, gauche-, and trans configurations across each of the two bonds constituting the linkage. These conformations were subjected to a combined MD/EM refinement using the NOESY derived constraints as pseudoenergy functions. Families of conformations for the whole molecule were then constructed from the structures derived for each linkage. This procedure was demonstrated on a fragment from the carbohydrate-protein linkage region of connective tissue proteoglycans.