title: The flexibility of the Le(a)Le(x) tumor associated antigen central fragment studied by systematic and stochastic searches as well as dynamic simulations.
abstract: The solution conformational behavior of the Tumor-Associated Carbohydrate Antigen Le(a)Le(x) central fragment: methyl alpha-L-fucopyranosyl-(1-->4)-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1-->3)-beta-D-galactopyranoside was studied using three computational methods: a rigid systematic search as implemented in Sybyl, a stochastic search as implemented in MOE2004, and dynamics simulations using the SANDER module of AMBER9. Our results illustrate the complementarity of these methods to identify energetically relevant conformations and flexible linkages. In particular, the beta-GlcNAc-(1-->3)-Gal linkage was shown to be extremely flexible adopting a wide range of orientations around two energy minima. The modeling results were validated by comparison of theoretical distances, derived from the simulations, with experimental measurements obtained from 1D selective ROESY buildup curves on the synthetic fragment.
authors.affiliation: Department of Chemistry, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Trudy A
authors.initials: TA
authors.lastname: Jackson
authors.forename: Valerie
authors.initials: V
authors.lastname: Robertson
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: France-Isabelle
authors.initials: FI
authors.lastname: Auzanneau
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003198:Computer Simulation; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D013269:Stochastic Processes; D013816:Thermodynamics; D014312:Trisaccharides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D009844:Oligosaccharides; D014312:Trisaccharides; C111125:lewis(a)-lewis(x)