Atomic Details of Carbon-Based Nanomolecules Interacting with Proteins

Costanzo, Luigi Di; Geremia, Silvano

doi:10.3390/molecules25153555

Cited by 17 publications

(15 citation statements)

References 147 publications

(199 reference statements)

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“…Supramolecular approaches can preserve these properties [ 19 ]. Recently, it was demonstrated that it is possible to use peptides [ 20 ] and proteins [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] as supramolecular hosts for the non-covalent dispersion of fullerenes [ 21 ]. Different proteins, such as albumins [ 22 , 23 ], lysozyme [ 23 , 24 , 25 , 26 ], pepsin [ 27 ], trypsin [ 27 ], or natural protein surfactants [ 28 ] were used for the mono-molecular dispersion of pristine fullerenes in a physiological environment.…”

Section: Introductionmentioning

confidence: 99%

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

Marforio

Calza

Mattioli

et al. 2021

IJMS

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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.

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Section: Introductionmentioning

confidence: 99%

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

Marforio

Calza

Mattioli

et al. 2021

IJMS

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“…The atomistic understanding of the interactions of C 60 with SARS-CoV-2 M pro is crucial for real applications of nanomolecules in medicine [ 26 ]. MD simulations represent a powerful tool to investigate such interactions [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

“…Fullerenes and carbon nanomaterials are able to interact with peptides [ 16 , 17 ] and proteins [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ] and, in general, are considered promising antiviral agents [ 27 , 28 , 29 , 30 , 31 , 32 ]. The idea of using C 60 as an inhibitor of the HIV protease dates back to 1993 [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Fullerenes against COVID-19: Repurposing C60 and C70 to Clog the Active Site of SARS-CoV-2 Protease

et al. 2022

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The persistency of COVID-19 in the world and the continuous rise of its variants demand new treatments to complement vaccines. Computational chemistry can assist in the identification of moieties able to lead to new drugs to fight the disease. Fullerenes and carbon nanomaterials can interact with proteins and are considered promising antiviral agents. Here, we propose the possibility to repurpose fullerenes to clog the active site of the SARS-CoV-2 protease, Mpro. Through the use of docking, molecular dynamics, and energy decomposition techniques, it is shown that C60 has a substantial binding energy to the main protease of the SARS-CoV-2 virus, Mpro, higher than masitinib, a known inhibitor of the protein. Furthermore, we suggest the use of C70 as an innovative scaffold for the inhibition of SARS-CoV-2 Mpro. At odds with masitinib, both C60 and C70 interact more strongly with SARS-CoV-2 Mpro when different protonation states of the catalytic dyad are considered. The binding of fullerenes to Mpro is due to shape complementarity, i.e., vdW interactions, and is aspecific. As such, it is not sensitive to mutations that can eliminate or invert the charges of the amino acids composing the binding pocket. Fullerenic cages should therefore be more effective against the SARS-CoV-2 virus than the available inhibitors such as masinitib, where the electrostatic term plays a crucial role in the binding.

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“…Metal coordination is a specific and directional interaction, widely used to control protein assembly and crystallization. − Highlights include the metal-directed assembly of monomeric protein building blocks into cages. − The metallo-construction of these polyhedra enables controlled assembly and disassembly via multiple stimuli. Controlled protein assembly can be achieved also by water-soluble macrocycles that act as “molecular glues”. − Bioorganic crystalline hybrids of protein and calix[ n ]arenes − or cucurbit[ n ]urils − have been reported. While metal coordination and macrocycle complexation have been used separately to direct protein assembly, the combination of these two approaches has not been explored.…”

Section: Introductionmentioning

confidence: 99%

Metal-Mediated Protein–Cucurbituril Crystalline Architectures

Guagnini

Engilberge

Flood

et al. 2020

Crystal Growth & Design

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Controlled protein assembly is an enabling technology, for example, in the bottom-up fabrication of biomaterials. This paper describes the assembly of a β-propeller protein using two orthogonal interaction modes. Previously, protein assembly was directed by metal coordination or macrocycle complexation. Here, we demonstrate the combination of metal coordination and macrocycle complexation for controlled assembly. An established protein−cucurbit[7]uril (Q7) assembly, which relies on trimeric Q7 clusters, was modified by the inclusion of metal-binding sites in the protein. The application of zinc−histidine coordination to tune the Q7-induced assembly resulted in metallo-bioorganic crystalline architectures. The relative arrangement of the protein−Q7 layers was reorganized by the zinc bridging ions. One structure resulted in a different type of protein−Q7 packing that involves Q7 dimers. Apparently, Q7 is a versatile molecular glue that can be combined with metal-mediated protein assembly. This dual strategy expands significantly the toolkit for engineered assembly.

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Atomic Details of Carbon-Based Nanomolecules Interacting with Proteins

Cited by 17 publications

References 147 publications

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

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

Fullerenes against COVID-19: Repurposing C60 and C70 to Clog the Active Site of SARS-CoV-2 Protease

Metal-Mediated Protein–Cucurbituril Crystalline Architectures

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