[NMR paper] A molecular dynamics simulations-based interpretation of NMR multidimensional heteronuclear spectra of alpha-synuclein/dopamine adducts.

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A molecular dynamics simulations-based interpretation of NMR multidimensional heteronuclear spectra of alpha-synuclein/dopamine adducts.

Related Articles A molecular dynamics simulations-based interpretation of NMR multidimensional heteronuclear spectra of alpha-synuclein/dopamine adducts.

Biochemistry. 2013 Aug 21;

Authors: Dibenedetto D, Rossetti G, Caliandro R, Carloni P

Abstract
Multidimensional heteronuclear NMR spectroscopy provides valuable structural information on adducts between naturally unfolded proteins and their ligands. These are often of high pharmacological relevance. Unfortunately, the determination of the contributions to observed chemical shifts changes upon ligand binding is difficult. Here we present a tool that uses molecular dynamics (MD) trajectories to help interpret 2D NMR data. We apply this tool to the naturally unfolded protein human ?-synuclein interacting with dopamine, an inhibitor of fibril formation, and with its oxidation products in water solution. By coupling 2D NMR experiments with MD simulations of the adducts in explicit water, the tool confirms that the ligands bind preferentially to 125YEMPS129 residues in the C-terminal and, to few residues of the so-called NAC region, consistently with experimental data. It also suggests that the ligands might cause conformational rearrangements of distal residues located at the N-terminal. Hence, performed analysis provides a rationale for the observed changes in chemical shifts in terms of direct contacts with the ligand and conformational changes of the protein.


PMID: 23964651 [PubMed - as supplied by publisher]



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