ABSTRACT
Numerous experiments have revealed that fullerene (C60) and its derivatives can bind to proteins and affect their biological functions. In this study, we explored the interaction between fullerine and the ß2-adrenergic receptor (ß2AR). The MD simulation results show that fullerene binds with the extracellular loop 2 (ECL2) and intracellular loop 2 (ICL2) of ß2AR through hydrophobic interactions and π-π stacking interactions. In the C60_in1 trajectory, due to the π-π stacking interactions of fullerene molecules with PHE and PRO residues on ICL2, ICL2 completely flipped towards the fullerene direction and the fullerene moved slowly into the lipid membrane. When five fullerene molecules were placed on the extracellular side, they preferred to stack into a stable fullerene cluster (a deformed tetrahedral aggregate), and had almost no effect on the structure of ß2AR. The hydroxyl groups of fullerene derivatives (C60(OH)X, X represents the number of hydroxyl groups, X = 4, 8) can form strong hydrogen bonds with the ECL2, helix6, and helix7 of ß2AR. The hydroxyl groups firmly grasp the ß2AR receptor like several claws, blocking the binding entry of ligands. The simulation results show that fullerene and fullerene derivatives may have a significant effect on the local structure of ß2AR, especially the distortion of helix4, but bring about no great changes within the overall structure. It was found that C60 did not compete with ligands for binding sites, but blocked the ligands' entry into the pocket channel. All the above observations suggest that fullerene and its derivatives exhibit certain cytotoxicity.
