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Conformational behavior of nucleotide–sugar in solution: Molecular dynamics and NMR study of solvated uridine diphosphate–glucose in the presence of monovalent cations
Author(s) -
Petrová Pavla,
Monteiro Céline,
Hervé du Penhoat Catherine,
Koča Jaroslav,
Imberty Anne
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(200106)58:7<617::aid-bip1035>3.0.co;2-1
Subject(s) - chemistry , molecular dynamics , aqueous solution , nucleotide , pyrophosphate , nucleotide sugar , sugar phosphates , ribose , nuclear magnetic resonance spectroscopy , nuclear overhauser effect , molecule , computational chemistry , stereochemistry , phosphate , organic chemistry , enzyme , biochemistry , gene
The nucleotide–sugars are metabolites of primary importance in the biosynthesis of polysaccharides and glycoconjugates since they serve as sugar donors in the reactions of glycosyltransferases, enzymes that displays a high specificity for both donors and acceptors. In order to determine the conformational behavior of uridinediphosphoglucose in dilute aqueous solution that includes a physiologically relevant concentration of salt, parallel NMR and molecular modeling investigations have been conducted. Nine molecular dynamics trajectories of 3 ns each were calculated in presence of explicit water and monovalent cations with the use of the AMBER force field with recently developed energy parameters for nucleotide–sugars (P. Petrova, J. Koča, and A. Imberty, Journal of American Chemical Society, 1999 , vol. 121, pp. 5535–5547 ). Theoretical nuclear Overhauser effect data were calculated from these simulations using a model‐free approach that takes into account internal motions. Comparison of theoretical and experimental data gives excellent agreement for the region surrounding the glucose–phosphate linkage including the pyrophosphate linkage itself. Less satisfactory agreement is obtained for the ribose ring and the base orientations. On the whole, both NMR and molecular dynamics simulations predict the molecule to be flexible, and to visit a large number of conformations while maintaining an extended overall shape. © 2001 John Wiley & Sons, Inc. Biopolymers 58: 617–635, 2001