Structural and dynamic properties of monoclonal antibodies immobilized on CNTs: A computational study

Federica De Leo, Jacopo Sgrignani, Davide Bonifazi, Alessandra Magistrato

Résultats de recherche: Contribution à un journal/une revueArticle

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Résumé

Due to the widespread application of carbon nanotube (CNT)-based materials in nanomedicine, it is nowadays of paramount importance to unravel at the atomistic level of detail the structural properties of such bioconjugates in order to rationalize and predict the effect exerted by the graphitic framework on the bio-active counterpart. In this paper, we report for the first time all-atom explicit solvent molecular dynamics (MD) simulations investigating the structural and dynamic properties of a noncovalent bioconjugate in which the monoclonal Cetuximab antibody (Ctx) is adsorbed on a CNT surface. Upon selection of the three most representative adsorption modes as obtained by docking studies, force-field MD and DFT simulations unambiguously showed that hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. Two main adsorption poses have been predicted: a pose-fab (p-fab) and pose-fc (p-fc) (fab = fragment antigen binding region; fc = fragment crystallizable region), the former being favored with small-diameter tubes (≤40 Å). In all the predicted poses, the secondary structure of Ctx is largely unaffected by the presence of the graphitic surface and, consistently with previous literature studies, our simulations reveal that positively charged amino acidic residues, such as Lys and Arg, predominantly contribute to the stabilization of the CNT×Ctx complex acting like surfactants. The predicted structural models are consistent with the experimental data, for which the immobilization of the antibody on CNTs does not disrupt the structural and recognition properties of the Ctx, consequently supporting the reliability of the used bioconjugation strategy for engineering stable and responsive hybrid nanomaterials for therapeutic applications. Moreover, a remarkable structural similarity of Ctx with antibodies of different isotypes suggests that in principle the CNT framework can interact in the same manner with all antibodies currently used in clinical applications. Antibodies and carbon nanotubes (CNT): Molecular dynamics simulations on the structural and dynamic properties of an antibody interfacing with a CNT surface showed that the hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. The predicted structural models are consistent with the experimental data, supporting the reliability of the bioconjugation strategy for engineering active hybrid nanomaterials for therapeutic applications.

langue originaleAnglais
Pages (de - à)12281-12293
Nombre de pages13
journalChemistry: A European Journal
Volume19
Numéro de publication37
Les DOIs
étatPublié - 9 sept. 2013

Empreinte digitale

Monoclonal antibodies
Antibodies
Carbon Nanotubes
Monoclonal Antibodies
Carbon nanotubes
Molecular dynamics
Adsorption
Nanostructured materials
Proteins
Medical nanotechnology
Immunoglobulin Fc Fragments
Immunoglobulin Fab Fragments
Computer simulation
Antigens
Discrete Fourier transforms
Surface-Active Agents
Structural properties
Surface active agents
Stabilization
Atoms

Citer ceci

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abstract = "Due to the widespread application of carbon nanotube (CNT)-based materials in nanomedicine, it is nowadays of paramount importance to unravel at the atomistic level of detail the structural properties of such bioconjugates in order to rationalize and predict the effect exerted by the graphitic framework on the bio-active counterpart. In this paper, we report for the first time all-atom explicit solvent molecular dynamics (MD) simulations investigating the structural and dynamic properties of a noncovalent bioconjugate in which the monoclonal Cetuximab antibody (Ctx) is adsorbed on a CNT surface. Upon selection of the three most representative adsorption modes as obtained by docking studies, force-field MD and DFT simulations unambiguously showed that hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. Two main adsorption poses have been predicted: a pose-fab (p-fab) and pose-fc (p-fc) (fab = fragment antigen binding region; fc = fragment crystallizable region), the former being favored with small-diameter tubes (≤40 {\AA}). In all the predicted poses, the secondary structure of Ctx is largely unaffected by the presence of the graphitic surface and, consistently with previous literature studies, our simulations reveal that positively charged amino acidic residues, such as Lys and Arg, predominantly contribute to the stabilization of the CNT×Ctx complex acting like surfactants. The predicted structural models are consistent with the experimental data, for which the immobilization of the antibody on CNTs does not disrupt the structural and recognition properties of the Ctx, consequently supporting the reliability of the used bioconjugation strategy for engineering stable and responsive hybrid nanomaterials for therapeutic applications. Moreover, a remarkable structural similarity of Ctx with antibodies of different isotypes suggests that in principle the CNT framework can interact in the same manner with all antibodies currently used in clinical applications. Antibodies and carbon nanotubes (CNT): Molecular dynamics simulations on the structural and dynamic properties of an antibody interfacing with a CNT surface showed that the hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. The predicted structural models are consistent with the experimental data, supporting the reliability of the bioconjugation strategy for engineering active hybrid nanomaterials for therapeutic applications.",
keywords = "antibodies, carbon nanotubes, density functional calculations, hydrophobicity, molecular dynamics, supramolecular interactions",
author = "{De Leo}, Federica and Jacopo Sgrignani and Davide Bonifazi and Alessandra Magistrato",
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Structural and dynamic properties of monoclonal antibodies immobilized on CNTs : A computational study. / De Leo, Federica; Sgrignani, Jacopo; Bonifazi, Davide; Magistrato, Alessandra.

Dans: Chemistry: A European Journal, Vol 19, Numéro 37, 09.09.2013, p. 12281-12293.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Structural and dynamic properties of monoclonal antibodies immobilized on CNTs

T2 - A computational study

AU - De Leo, Federica

AU - Sgrignani, Jacopo

AU - Bonifazi, Davide

AU - Magistrato, Alessandra

PY - 2013/9/9

Y1 - 2013/9/9

N2 - Due to the widespread application of carbon nanotube (CNT)-based materials in nanomedicine, it is nowadays of paramount importance to unravel at the atomistic level of detail the structural properties of such bioconjugates in order to rationalize and predict the effect exerted by the graphitic framework on the bio-active counterpart. In this paper, we report for the first time all-atom explicit solvent molecular dynamics (MD) simulations investigating the structural and dynamic properties of a noncovalent bioconjugate in which the monoclonal Cetuximab antibody (Ctx) is adsorbed on a CNT surface. Upon selection of the three most representative adsorption modes as obtained by docking studies, force-field MD and DFT simulations unambiguously showed that hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. Two main adsorption poses have been predicted: a pose-fab (p-fab) and pose-fc (p-fc) (fab = fragment antigen binding region; fc = fragment crystallizable region), the former being favored with small-diameter tubes (≤40 Å). In all the predicted poses, the secondary structure of Ctx is largely unaffected by the presence of the graphitic surface and, consistently with previous literature studies, our simulations reveal that positively charged amino acidic residues, such as Lys and Arg, predominantly contribute to the stabilization of the CNT×Ctx complex acting like surfactants. The predicted structural models are consistent with the experimental data, for which the immobilization of the antibody on CNTs does not disrupt the structural and recognition properties of the Ctx, consequently supporting the reliability of the used bioconjugation strategy for engineering stable and responsive hybrid nanomaterials for therapeutic applications. Moreover, a remarkable structural similarity of Ctx with antibodies of different isotypes suggests that in principle the CNT framework can interact in the same manner with all antibodies currently used in clinical applications. Antibodies and carbon nanotubes (CNT): Molecular dynamics simulations on the structural and dynamic properties of an antibody interfacing with a CNT surface showed that the hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. The predicted structural models are consistent with the experimental data, supporting the reliability of the bioconjugation strategy for engineering active hybrid nanomaterials for therapeutic applications.

AB - Due to the widespread application of carbon nanotube (CNT)-based materials in nanomedicine, it is nowadays of paramount importance to unravel at the atomistic level of detail the structural properties of such bioconjugates in order to rationalize and predict the effect exerted by the graphitic framework on the bio-active counterpart. In this paper, we report for the first time all-atom explicit solvent molecular dynamics (MD) simulations investigating the structural and dynamic properties of a noncovalent bioconjugate in which the monoclonal Cetuximab antibody (Ctx) is adsorbed on a CNT surface. Upon selection of the three most representative adsorption modes as obtained by docking studies, force-field MD and DFT simulations unambiguously showed that hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. Two main adsorption poses have been predicted: a pose-fab (p-fab) and pose-fc (p-fc) (fab = fragment antigen binding region; fc = fragment crystallizable region), the former being favored with small-diameter tubes (≤40 Å). In all the predicted poses, the secondary structure of Ctx is largely unaffected by the presence of the graphitic surface and, consistently with previous literature studies, our simulations reveal that positively charged amino acidic residues, such as Lys and Arg, predominantly contribute to the stabilization of the CNT×Ctx complex acting like surfactants. The predicted structural models are consistent with the experimental data, for which the immobilization of the antibody on CNTs does not disrupt the structural and recognition properties of the Ctx, consequently supporting the reliability of the used bioconjugation strategy for engineering stable and responsive hybrid nanomaterials for therapeutic applications. Moreover, a remarkable structural similarity of Ctx with antibodies of different isotypes suggests that in principle the CNT framework can interact in the same manner with all antibodies currently used in clinical applications. Antibodies and carbon nanotubes (CNT): Molecular dynamics simulations on the structural and dynamic properties of an antibody interfacing with a CNT surface showed that the hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. The predicted structural models are consistent with the experimental data, supporting the reliability of the bioconjugation strategy for engineering active hybrid nanomaterials for therapeutic applications.

KW - antibodies

KW - carbon nanotubes

KW - density functional calculations

KW - hydrophobicity

KW - molecular dynamics

KW - supramolecular interactions

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