α-synuclein is a small 14 kDA acidic protein found mainly in the neuronal tissue and plays an important role in the pathogenesis of Parkinson's disease. α-synuclein is an intrinsically disordered protein, with little or no structure in its native state. Also known as the protein-chameleon α-synuclein is known to adapt its secondary structure depending on the surrounding environment. It is mainly disordered in a solvent, it can curl into α helices near membranes and stretch into β-sheets in fibrils or amyloids. This protein can accumulate and give rise to higher order insoluble aggregates which can lead to the triggering of Parkinson's disease.

We have developed a highly coarse grained model to study the aggregation of α-synuclein. We model a protein as a chain of twelve particles that can change their internal states, and therby shape and interaction parameters, in response to the environment. A protein in the disordered state is modelled as a random chain of soft spheres. By transformations of some of the particles into spherocylinders and by rearrangement into a planar configuration, the protein can adopt an ordered state capable of forming fibrils.

In a first representation we coarse grained a protein into a single polymorph patchy-particle, that can change conformation depending on the environment. Simulation results show the formation of oligomers and fibrils by a direct nucleation-and-growth mechanism, by two-step-nucleation through the conversion of an oligomer into a fiber or vice versa, and by fibril-enhanced conversion of oligomers into fibrils[1].