Molecular Basis of Small-Molecule Binding to α-Synuclein

Key Points

• Investigate the molecular and structural basis of small-molecule binding to the disordered protein alpha-synuclein using computational and experimental methods.
• Conducted molecular dynamics (MD) simulations to characterize interaction mechanisms and binding conformations between small molecules and alpha-synuclein.
• Validated predicted binding affinities and key structural interaction features using nuclear magnetic resonance (NMR) spectroscopy experiments.
• Molecular dynamics simulations successfully resolved binding affinities and core structural features governing small-molecule interaction with alpha-synuclein.
• Experimental NMR measurements corroborated the computational predictions, demonstrating the utility of MD simulations in rationally designing small molecules for disordered proteins.