Dissecting the Supramolecular Dispersion of Fullerenes by Proteins/Peptides: Amino Acid Ranking and Driving Forces for Binding to C60.

Tainah Dorina Marforio,Francesco Zerbetto,Edoardo Jun Mattioli,Matteo Calvaresi,Alessandro Calza

doi:10.3390/ijms222111567

Tainah Dorina Marforio, Francesco Zerbetto + Show 3 more

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https://doi.org/10.3390/ijms222111567

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Abstract

Molecular dynamics simulations were used to quantitatively investigate the interactions between the twenty proteinogenic amino acids and C60. The conserved amino acid backbone gave a constant energetic interaction ~5.4 kcal mol−1, while the contribution to the binding due to the amino acid side chains was found to be up to ~5 kcal mol−1 for tryptophan but lower, to a point where it was slightly destabilizing, for glutamic acid. The effects of the interplay between van der Waals, hydrophobic, and polar solvation interactions on the various aspects of the binding of the amino acids, which were grouped as aromatic, charged, polar and hydrophobic, are discussed. Although π–π interactions were dominant, surfactant-like and hydrophobic effects were also observed. In the molecular dynamics simulations, the interacting residues displayed a tendency to visit configurations (i.e., regions of the Ramachandran plot) that were absent when C60 was not present. The amino acid backbone assumed a “tepee-like” geometrical structure to maximize interactions with the fullerene cage. Well-defined conformations of the most interactive amino acids (Trp, Arg, Met) side chains were identified upon C60 binding.

Highlights

In biomedical applications, fullerenes have wide potential [1,2,3] due to their (i) antioxidant and radical scavenging capacity; (ii) neuroprotective action; iii) biological activity as antiviral, antibacterial, antiapoptotic molecules; (iv) enzyme inhibition activity; (v) photosensitizing ability in photodynamic anticancer and antimicrobic therapy; (vi) capacity as contrast agents; and (vii) drug and gene delivery ability
The amino acids were capped by acetyl (ACE) and n-methyl amide (NME) groups at the N- and C-termini (ACE-AA-NME), (Scheme 1) to reproduce the typical interactions between C60 and an amino acid inserted into the peptide/protein sequence
We describe in detail the Mechanics/Generalized Born Surface Area (MM/GBSA) ranking, 2.1

Summary

Introduction

Fullerenes have wide potential [1,2,3] due to their (i) antioxidant and radical scavenging capacity; (ii) neuroprotective action; iii) biological activity as antiviral, antibacterial, antiapoptotic molecules; (iv) enzyme inhibition activity; (v) photosensitizing ability in photodynamic anticancer and antimicrobic therapy; (vi) capacity as contrast agents; and (vii) drug and gene delivery ability. The extreme hydrophobic nature of fullerenes [4] has, prevented their biological application, making them of scarce bioavailability in physiological environments. Initial studies of the biological activity of fullerenes involved the functionalization of the hydrophobic cage with hydrophilic moieties to enhance their water solubility [5,6]. The most appealing fullerene derivatives for biological applications are fullerene–biomolecule conjugates [11], such as fulleroamino acids and fulleropeptides [12,13,14,15], in which the functionalization moiety is both hydrophilic and biocompatible. Fulleroamino acids and fulleropeptides are at least partially water soluble, and demonstrated high biological and pharmacological activities [12,13,14,15]. Fullerenes were chemically conjugated to proteins [15,16,17] such as azurin [16], thyroglobulin [17], and albumins [17] to improve their functionality (electronic communication or targeting) and biocompatibility

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