Molecular Dynamics Simulations of Alpha-synuclein

POSTER

Abstract

We investigate the conformational dynamics of single alpha-synuclein proteins, which have been implicated in amyloid diseases such as Parkinson's and Alzheimer's disease, in solution using unconstrained and constrained all-atom, explicit solvent molecular dynamics simulations. The constraints on inter-residue separations are obtained from our single-molecule FRET measurements of eleven FRET pairs that span the protein. By comparing the simulation data satisfying different combinations of FRET constraints, we are able to identify those constraints that are most important in determining the radius of gyration and key features of the contact map of the protein.

Authors

  • Maria Sammalkorpi

    • Departments of Chemical Engineering, Physics, Mechanical Engineering and Materials Science, and Molecular Biophysics and Biochemistry, Yale University
    • Dept. of Chemical Engineering, Yale University

  • Carl Schreck

    • Departments of Chemical Engineering, Physics, Mechanical Engineering and Materials Science, and Molecular Biophysics and Biochemistry, Yale University
    • Department of Physics
    • Yale University
    • Yale

  • Abhinav Nath

    • Departments of Chemical Engineering, Physics, Mechanical Engineering and Materials Science, and Molecular Biophysics and Biochemistry, Yale University

  • David DeWitt

    • Departments of Chemical Engineering, Physics, Mechanical Engineering and Materials Science, and Molecular Biophysics and Biochemistry, Yale University

  • Elizabeth Rhoades

    • Departments of Chemical Engineering, Physics, Mechanical Engineering and Materials Science, and Molecular Biophysics and Biochemistry, Yale University

  • Corey O'Hern

    • Yale University
    • Departments of Chemical Engineering, Physics, Mechanical Engineering and Materials Science, and Molecular Biophysics and Biochemistry, Yale University
    • Yale