In silico search of protein targets for fullerenes

Abstract

Fullerenes are a group of nanomaterials with an extensive range of applications, but little is known about the effects on biochemical processes linked to these nanoparticles. For these reason, the innovative techniques of virtual screening and molecular docking were applied to search for target proteins and discuss the fullerene exposure effects on these proteins functions and behavior. PatchDock software was employed to calculate the theoretical affinity through the atomic contact energy (ACE) of C60 fullerene, C70 fullerene and their respective derivatives of propanedioic acid and 1,2 diphenylethanol docked to 118 proteins structures previously selected from the potential drug target database (PDTD). Glucocorticoid receptor and estrogen receptor alpha (PDB code: 1NHZ and 3ERT respectively) showed the most remarkable affinity value when docked with all optimized fullerene structures specially C70-Diphenyleathanol which achieved -50.43 kcal/mol and - 40.22 kcal/mol with each protein, values much higher than those achieved by the 1NHZ well known inhibitor antiprogestin mifepristone (RU486) (-15.75 kcal/mol) and 3ERT inhibitor 4-Hidroxitamoxifen (-13.76 kcal/mol). Whereas, these proteins have been related with hormonal function, eukaryotic gene expression and mental illnesses such as psychotic depression, bipolar disorder and schizophrenia a precedent for the possible treatment of these diseases using fullerene derivatives for protein inhibition is here establish. PatchDock ACE results for several fullerenes derivatives significantly correlated with reported median inhibitory concentrations (R2 = 0.6135, P<0.0125), supporting the computational reliability of the prediction made by our docking simulations.