↵ 1 Present address: University of Michigan, Dept. of Neurology, 109 Zina Pitcher Pl., Ann Arbor, MI 48109.

Department of Physics and Astronomy, Michigan State University, 567 Wilson Rd. Rm 4227, East Lansing, MI 48824.

Background: The molecular tweezer, CLR01, binds to Lys and prevents aggregation of α-synuclein.

Results: CLR01 binds directly to monomeric α-synuclein near the N terminus and changes the charge distribution in the sequence, swelling the chain, and increasing the protein reconfiguration rate.

Conclusion: Aggregation is inhibited by making the protein more diffusive.

Significance: The most effective aggregation inhibitors may change monomer dynamics rather than structure.