Interaction of C₆₀-Fullerene and Carboxyfullerene with Proteins:  Docking and Binding Site Alignment

Abstract

The unique properties of fullerenes have raised the interest of using them for biomedical applications. Within this framework, the interactions of fullerenes with proteins have been an exciting research target, yet little is known about how native proteins can bind fullerenes, and what is the nature of these interactions. Moreover, though some proteins have been shown to interact with fullerenes, up to date, no crystal structure of such complexes was obtained. Here we report docking studies aimed at examining the interactions of fullerene in two forms (C60 nonsubstituted fullerene and carboxyfullerene) with four proteins that are known to bind fullerene derivatives: HIV protease, fullerene-specific antibody, human serum albumin, and bovine serum albumin. Our work provides docking models with detailed binding pockets information, which closely match available experimental data. We further compare the predicted binding sites using a novel multiple binding site alignment method. A high similarity between the physicochemical properties and surface geometry was found for fullerene's binding sites of HIV protease and the human and bovine serum albumins.

Rapid insight into C60 influence on biological functions of proteins

“…Albumin From four main (highly populated) binding pockets detected for albumin-C 60 model, the lowest energy location stays in an agreement with literature data [31] (see Table 1 and Fig. 4).…”

“…Binding sites on HSA for nC 60 occurred similar to these for separate molecules. The same type of binding sites as was reported for interactions C 60 -albumin [31] were experimentally detected in nC 60 -albumin complexes [32]. These observations indicate that even though investigations of separate C 60 molecules are not complete as they should be for nC 60 , they bring reliable results, which can be extended on protein-nC 60 complexes.…”

“…4). This ligand position (ranked 3rd according to location occupancy,~11% population) is equal to the type 1 binding site described by Benyamini et al [31]. The location of the C 60 close to the type 2 binding site introduced by those authors was also found with our calculation but its rank was too low (about 5% of the population).…”

“…For two of the examined proteins, previously published data exist regarding fullerene or fullerenol binding sites: human serum albumin (HSA) [31,57,58] and hen-egg white lysozyme with fullerenol C 60 (OH)x (x≈24) [50] and pristine fullerene C60 [59]. Thus, albumin-C60 and lysozyme-C60 complexes were used as a validation set.…”

Molecular Interactions of Fullerene Derivatives in Human Serum and Inflammatory Cells

“…While others have investigated protein-binding techniques using fullerenes, including human serum (11)(12)(13)(14)(15), there is still little information regarding the identification of protein binding interactions. Here, it was demonstrated that TGA interacted with a wide range of proteins in human serum.…”