$\alpha -$synuclein under the magnifying glass. Insights from atomistic and coarse-grain simulations.

Neurodegenerative diseases are linked to the accumulation of misfolded intrinsically disordered proteins in the brain. Here, we use both all-atom and coarse-grain simulations to explore the intricate dynamics and the aggregation of $\alpha $-synuclein, the protein implicated in Parkinson's disease. We explore the free energy landscapes of $\alpha $-synuclein by using Molecular Dynamics simulations and extract information on the structure of the protein as well as on its binding affinities[1]. Next, to study the aggregation, we proceed with representing $\alpha $-synuclein as a chain of deformable particles that can adapt their geometry, binding affinities and can rearrange into different disordered and ordered structures[2,3]. We use Brownian Dynamics to simulate the translational and rotational motions of the particles[4], as well as their interaction properties[2]. The simulations show valuable insight into the internal dynamics of $\alpha $-synuclein[1] and the formation of ordered and disordered aggregates[2]. In addition, the study is extended to investigate the attachment and folding of a protein to a fiber[3]. [1]I.M.Ilie, D.Nayar, W.K.den Otter, N.F.A.van der Vegt {\&} W.J.Briels, in prep [2]I.M.Ilie, W.K.den Otter and W.J.Briels, JCP 144, 085103 (2016) [3]I.M.Ilie, W.K.den Otter and W.J.Briels, in prep [4]I.M.Ilie, W.J.Briels and W.K.den Otter, JCP 142, 114103 (2015)