The flexibility of the LeaLex Tumor Associated Antigen central fragment studied by systematic and stochastic searches as well as dynamic simulations

The solution conformational behavior of the Tumor-Associated Carbohydrate Antigen LeaLex central fragment: methyl α-l-fucopyranosyl-(1→4)-2-acetamido-2-deoxy-β-d-glucopyranosyl-(1→3)-β-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 β-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.

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