Premium
Solution structure of hyaluronic acid oligomers by experimental and theoretical NMR, and molecular dynamics simulation
Author(s) -
Donati Alessandro,
Magnani Agnese,
Bonechi Claudia,
Barbucci Rolando,
Rossi Claudio
Publication year - 2001
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/1097-0282(200111)59:6<434::aid-bip1048>3.0.co;2-4
Subject(s) - chemistry , glycosidic bond , molecular dynamics , hydrogen bond , nuclear magnetic resonance spectroscopy , molecule , amide , nmr spectra database , carboxylate , two dimensional nuclear magnetic resonance spectroscopy , intramolecular force , relaxation (psychology) , aqueous solution , proton nmr , computational chemistry , crystallography , stereochemistry , spectral line , organic chemistry , psychology , social psychology , physics , astronomy , enzyme
The conformational properties of hyaluronic acid (HA) oligomers in aqueous solution were investigated by combining high‐resolution NMR experimental results, theoretical simulation of NMR two‐dimensional (2D) spectra by Complete Relaxation Matrix Analysis (CORMA), and molecular dynamics calculations. New experimental findings recorded for the tetra‐ and hexasaccharides enabled the stiffness of the HA and its viscoelastic properties to be interpreted. In particular, rotating frame nuclear Overhauser effect spectroscopy spectra provided new information about the arrangement of the glycosidic linkage. From 13 C NMR relaxation the rotational correlation time (τ c ) were determined. The τ c were employed in the calculation of geometrical constraints, by using the MARDIGRAS algorithm. Restrained simulated annealing and 1 ns of unrestrained molecular dynamic simulations were performed on the hexasaccharide in a box of 1215 water molecules. The β(1 → 3) and β(1 → 4) glycosidic links were found to be rigid. The lack of rotational degree of freedom is due to direct and/or water‐mediated interresidue hydrogen bonding. Both single or tandem water bridges were found between carboxylate group and N‐acetil group. The carboxylate group of glucuronic acid is not involved in a direct link with the amide group of N‐acetyl glucosamine and this facilitated bonding between the residue and the water molecules. © 2001 John Wiley & Sons, Inc. Biopolymers 59: 434–445, 2001