title: Assigning kinetic 3D-signatures to glycocodes.
abstract: Reconciling glycocodes and their associated bioactivities, via 3D-structure, will rationalise burgeoning high-throughput functional glycomics data and underpin a new era of opportunity in chemical biology. A major impasse to achieving this goal is a detailed understanding of pyranose sugar ring 3D-conformation (or pucker) and the affiliated microsecond-timescale exchange kinetics. Here, we perform hardware-accelerated kinetically-rigorous equilibrium simulations of fundamental monosaccharides to produce the hypothesis that pyranoses have microsecond-timescale kinetic puckering signatures in water, classified as unstable (rare in the glycome), metastable (infrequently observed) and stable (prevalent). The predicted μs-metastability of β-d-glucose explained hitherto irreconcilable experimental measurements. Twisted puckers seen in carbohydrate enzymes were present in the aqueous 3D-ensemble (suggesting preorganization) and pyranose-water interactions accounted for the relative stability of β-d-galactose. Characteristic 3D-shapes for biologically- and commercially-important carbohydrates and new rules linking chemical modifications with pyranose μs-puckering kinetics are proposed. The observations advance structural-glycomics towards dynamic 3D-templates suitable for structure-based design.
authors.affiliation: Faculty of Life Sciences, Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Benedict M
authors.initials: BM
authors.lastname: Sattelle
authors.forename: Andrew
authors.initials: A
authors.lastname: Almond
mesh_terms: D002236:Carbohydrate Conformation; D005947:Glucose / Q000737:chemistry*; D007700:Kinetics; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D005947:Glucose