Journal Article

FZJ-2015-03402

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Molecular Dynamics Simulation-Based Interpretation of Nuclear Magnetic Resonance Multidimensional Heteronuclear Spectra of α-Synuclein·Dopamine Adducts

Dibenedetto, D. ; Rossetti, G. (Corresponding Author)FZJ* ; Caliandro, R. ; Carloni, P.FZJ*

2013
American Chemical Society Columbus, Ohio

This record in other databases:      

Please use a persistent id in citations: doi:10.1021/bi400367r

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

---

Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Jülich Supercomputing Center (JSC)
3. GRS (GRS)

Research Program(s):

1. 411 - Computational Science and Mathematical Methods (POF2-411) (POF2-411)

---

Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---