Evaluation of implicit solvent models in molecular dynamics simulation of α-Synuclein

We report conventional and accelerated molecular dynamics simulations of alpha-Synuclein, designed to assess performance of using different starting conformation, solvation environment and force field combination. Backbone and sidechain chemical shifts, radius of gyration, presence of beta-hairpin structures in KTK(E/Q)GV repeats and secondary structure percentages were used to evaluate how variations in forcefield, solvation model and simulation protocol provide results that correlate with experimental findings. We show that with suitable choice of forcefield and solvent, ff03ws and OBC implicit model, respectively, acceptable reproduction of experimental data on size and secondary structure is obtained by both conventional and accelerated MD. In contrast to the implicit solvent model, simulations in explicit TIP4P/2005 solvent do not properly represent size or secondary structure of alpha-Synuclein.

Automated summary

Conventional and accelerated molecular dynamics simulations of alpha-Synuclein were performed to evaluate the impact of different starting conformations, solvation environments, and force field combinations. The study found that the choice of force field and solvent significantly influenced the size and secondary structure reproduction of alpha-Synuclein, with acceptable results obtained using ff03ws force field and OBC implicit solvent model.