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

Abstract

We report conventional and accelerated molecular dynamics simulations of α-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 β-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 α-Synuclein.

Communicated by Ramaswamy H. Sarma

Keywords:

• Parkinson’s disease
• synuclein
• molecular dynamics
• implicit solvent
• β-hairpins

Acknowledgements

We acknowledge the role of Advanced Research Computing @ Cardiff (ARCCA) in providing computational resources for simulations.

Disclosure statement

No potential conflict of interest was reported by the authors.