Structure and dynamics of a peptidoglycan monomer in aqueous solution using NMR spectroscopy and simulated annealing calculations

Hans Matter, László Szilágyi, P. Forgó, Željko Marinić, Branimir Klaić

Research output: Contribution to journalArticle

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Abstract

The conformation of the peptidoglycan monomer (PGM) from Brevibacterium divaricatum was determined in aqueous solution using a combined approach by 2D NMR spectroscopy, restrained simulated annealing, and molecular dynamics (MD) calculations. MD simulations in water without experimental constraints provided insights into the structure and dynamics of this glycopeptide. Hierarchical cluster analyses for conformer classifications were performed using a global molecular shape descriptor (CoMFA steric fields). Principal component analysis was subsequently employed to extract orthogonal principal conformational properties. Correlated dihedral angle mobilities were identified using a dynamic cross correlation map. The calculation of radial distribution functions for all polar protons of the molecule leads to additional information about the solvation of PGM in a protic solvent, while autocorrelation functions for dihedral angle fluctuations were used to monitor dynamic processes in different regions. From simulated annealing, a set of 11 conformers was obtained, all characterized by a well-defined extended N-terminal peptide part additionally stabilized by the bound disaccharide; the C-terminal part, on the other hand, exhibits more conformational flexibility in agreement with experimental data and MD simulations. The disaccharide conformation is in agreement with the conformational minimum computed for the model disaccharide 3-O-Me-4-O-βGlcNAc-μMurNAc using various force fields. Not only the interglycosidic bond but also the glycopeptide linkage exists in a single, well-defined conformation, for which no conformational changes can be detected during the MD simulations. In contrast, conflicting experimental data for the N-acetyl group of GlcNAc could be explained using a conformer population analysis based on ROE intensities and coupling constants accounting for a conformational equilibrium with one dominantly populated rotamer.

Original languageEnglish
Pages (from-to)2212-2223
Number of pages12
JournalJournal of the American Chemical Society
Volume119
Issue number9
DOIs
Publication statusPublished - 1997

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Peptidoglycan
Molecular Dynamics Simulation
Simulated annealing
Nuclear magnetic resonance spectroscopy
Molecular dynamics
Disaccharides
Magnetic Resonance Spectroscopy
Monomers
Conformations
Glycopeptides
Dihedral angle
Computer simulation
Brevibacterium
Solvation
Principal Component Analysis
Autocorrelation
Principal component analysis
Peptides
Distribution functions
Cluster Analysis

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Structure and dynamics of a peptidoglycan monomer in aqueous solution using NMR spectroscopy and simulated annealing calculations. / Matter, Hans; Szilágyi, László; Forgó, P.; Marinić, Željko; Klaić, Branimir.

In: Journal of the American Chemical Society, Vol. 119, No. 9, 1997, p. 2212-2223.

Research output: Contribution to journalArticle

Matter, Hans ; Szilágyi, László ; Forgó, P. ; Marinić, Željko ; Klaić, Branimir. / Structure and dynamics of a peptidoglycan monomer in aqueous solution using NMR spectroscopy and simulated annealing calculations. In: Journal of the American Chemical Society. 1997 ; Vol. 119, No. 9. pp. 2212-2223.
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