title: Insights on the conformational properties of hyaluronic acid by using NMR residual dipolar couplings and MD simulations.
abstract: The conformational features of hyaluronic acid, a key polysaccharide with important biological properties, have been determined through the combined used of nuclear magnetic resonance (NMR) spectroscopy and molecular modeling techniques. A decasaccharide fragment of sodium hyaluronate (HA) was submitted to 3.5 ns of molecular dynamics in explicit water environment form. The same decasaccharide was prepared by hyaluronidase digestion for the experimental study. The approach consisted in the measurements of NMR residual dipolar coupling (RDC) which were used to filter the molecular dynamics data by retaining those structures which were in agreement with the experimental observations. Further analysis of the new conformer ensemble (HA(RDC)) and clustering the molecules with respect to their overall length led to seven representative structures, which were described in terms of their secondary motifs, namely the best fitting helix geometry. As a result, this protocol permitted the assessment that hyaluronic acid can adopt two different arrangements, which can be described by a three- or four-folded left-handed helix, with a higher occurrence of the first one.
authors.affiliation: Department of Organic Chemistry and Biochemistry, University of Napoli Federico II, Complesso Universitario Monte Sant'Angelo, Via Cintia 4, Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gargiulo
authors.forename: Maria A
authors.initials: MA
authors.lastname: Morando
authors.forename: Alba
authors.initials: A
authors.lastname: Silipo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
authors.forename: Serge
authors.initials: S
authors.lastname: Pérez
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Parrilli
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Cristina
authors.initials: C
authors.lastname: De Castro
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D006820:Hyaluronic Acid / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000276:Adjuvants, Immunologic; D006820:Hyaluronic Acid