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Abstract
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One notable phenomenon in the Parkinson’s disease (PD)
treatment is the identification of inhibitors of the self-assembly
of Alpha-Synuclein (AS) protein. Here, the interactions of two
herbal compounds of Curcumin (CUR) and Rosmarinic-acid (RA)
with the NAC domain of AS were investigated by the molecular
dynamics (MD) simulation method. More specifically, the
purpose of this study was to investigate the molecular aspects
and the inhibition mechanism of the considered molecules, as
well as evaluating their effectiveness in preventing the AS
aggregation process. The trajectories of MD simulations were
used to evaluate the structural properties of the simulated
systems and to infer qualitative and quantitative facts regarding the interactions between the considered ligands and the
NAC domains. In addition to the MD studies, the energetics of
the ligand-NAC domain interactions were studied by MM-PBSA
method. The free energy of binding and various contributions
to it, as modeled in the MM-PBSA method, were evaluated and
analyzed. The results were also analyzed in terms of the rate
and strength of ligand binding to the domains. These analyses
showed that RA could bind to the NAC domain faster, as
compared to CUR, while the latter binds to the domain more
strongly than the former does. However, overall, the results
imply that both CUR and RA could effectively bind to NAC
domains; so, they could be considered as candidates to reduce
the aggregation of AS or as potential drugs for PD.
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