engleski

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

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 (SA) 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 dynamical 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 dynamical processes in different regions. From simulated annealing a set of 11 conformers were 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-methyl-4-O-GlcNAc--MurNAc 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 counting for a conformational equilibrium with one dominantly populated rotamer.

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