title: Computational studies of the binding mechanisms of fullerenes to human serum albumin.
abstract: Fullerene and its derivatives show promising prospects for applications in a vast array of biological systems. A key aspect concerning their biomedical applications is how they interact with proteins from molecular levels, which is still poorly understood. In the current study, we investigated the structural and thermodynamic basis of the interactions between two pharmacologically relevant fullerene derivatives and human serum albumin (HSA) using molecular docking, molecular dynamics simulations, and binding free energy calculations. Our results demonstrate that fullerenes steadily bind with HSA at the interfacial cavity formed by subdomains IIA and IIIA. In agreement with available experimental data, our simulations show that the global structure of HSA becomes more compact in the presence of fullerene, while local structural dynamics of the binding cavity behaves diversely depending on the chemical properties of bound fullerenes. Binding free energy calculations confirmed that the interactions between fullerenes and HSA are dominantly stabilized by van der Waals forces and they further allowed the identification of key residues involved in fullerene binding. The structural and energetic insights obtained from this work may help for the development of fullerene-based drug delivery devices and therapeutic agents with improved biological profile.
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemistry and Chemical Engineering, Nanjing Tech University, Nanjing, 210009, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Li
authors.forename: Lizhi
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
mesh_terms: D001665:Binding Sites; D037741:Fullerenes / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D012709:Serum Albumin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D037741:Fullerenes; D012709:Serum Albumin