Molecular dynamic simulation of the conformation state of human micelle-bound alpha-synuclein protein in various concentrations of potassium

The misfolding of the protein alpha-synuclein (aS) has been implicated in the biochemical cascades of several neurodegenerative diseases, such as Parkinson's disease and Alzheimer's. The aS protein can naturally exist in a compacted or an extended conformation, but it is the extended shape that is most frequently associated with aggregation and the development of deleterious fibrils known as Lewy bodies, a common presentation in neurodegenerative diseases. Previous research has indicated that the presence of four potassium ions can effect an unwinding conformation in aS but has yet to determine whether the same extending effects are seen as potassium concentrations increase. The aim of this work was to investigate the modulating effects of various potassium ion concentrations on the conformation of aS in aqueous solutions. The aS protein was studied using molecular dynamics simulations run in the software GROMACS. Once the energy of the system was minimized and the system reached an equilibrium with respect to temperature and pressure, molecular dynamic (MD) simulations were run for fifteen nanoseconds with 0.002 fs steps. To expedite calculations, these simulations were performed in dodecahedral environments instead of the cube environments used in previous research as dodecahedrons have only seventy percent the volume of a cube. The radius of gyration was then measured to quantify any changes to the conformation of aS in the presence of zero, eight, sixteen, and thirty-two potassium ions. The goal of this research was to shed light on whether increasing potassium concentrations continue to effect an extended conformation in aS or if higher potassium ion levels reverse this effect, therapeutically returning the protein to a more compacted state.