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Copyright © 2021 Artur A. M. L. Brandt et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0/

Abstract

Peptide TT830-843 from the tetanus toxin is a universal T-cell epitope. It helps in vaccination and induces T-cell activation. However, the fine molecular interaction between this antigen and the major histocompatibility complex (MHC) remains unknown. Molecular analysis of its interaction with murine MHC (H-2) was proposed to explore its immune response efficiency. Molecular dynamics simulations are important mechanisms for understanding the basis of protein-ligand interactions, and metadynamics is a useful technique for enhancing sampling in molecular dynamics. SPR (surface plasmon resonance) assays were used to validate whether the metadynamics results are in accordance with the experimental results. The peptide TT830-843 unbinding process was simulated, and the free energy surface reconstruction revealed a detailed conformational landscape. The simulation described the exiting path as a stepwise mechanism between progressive detachment states. We pointed out how the terminus regions act as anchors for binding and how the detachment mechanism includes the opening of α-helices to permit the peptide’s central region dissociation. The results indicated the peptide/H-2 receptor encounter occurs within a distance lesser than 27.5 Å, and the encounter can evolve to form a stable complex. SPR assays confirmed the complex peptide/H-2 as a thermodynamically stable system, exhibiting enough free energy to interact with TCR on the antigen-presenting cell surface. Therefore, combining in silico and in vitro assays provided significant evidence to support the peptide/H-2 complex formation.

Details

Title
Combining Well-Tempered Metadynamics Simulation and SPR Assays to Characterize the Binding Mechanism of the Universal T-Lymphocyte Tetanus Toxin Epitope TT830-843
Author
Artur A M L Brandt 1   VIAFID ORCID Logo  ; Rodrigues-da-Silva, Rodrigo N 2   VIAFID ORCID Logo  ; Lima-Junior, Josué C 3   VIAFID ORCID Logo  ; Alves, Carlos R 4   VIAFID ORCID Logo  ; Franklin de Souza-Silva 5   VIAFID ORCID Logo 

 Faculdade de Educação Tecnológica do Estado do Rio de Janeiro, Rua Clarimundo de Melo, 847, CEP 21311-281, Rio de Janeiro, RJ, Brazil; Univeritas-Rio, Rua Marques de Abrantes, 55, CEP 2230-060, Rio de Janeiro, RJ, Brazil 
 Fundação Oswaldo Cruz, Instituto de Tecnologia em Imunobiológicos, Laboratório de Tecnologia Diagnóstica, Avenida Brasil, 4365, CEP 21040-900, Rio de Janeiro, RJ, Brazil 
 Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Imunoparasitologia, Avenida Brasil, 4365, CEP 21040-900, Rio de Janeiro, RJ, Brazil 
 Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Avenida Brasil, 4365, CEP 21040-900, Rio de Janeiro, RJ, Brazil 
 Centro de Desenvolvimento Tecnológico em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Universidade Iguaçu, Faculdade de Ciências Biológicas e da Saúde, Rio de Janeiro, RJ, Brazil 
Editor
Sebastien Fiorucci
Publication year
2021
Publication date
2021
Publisher
John Wiley & Sons, Inc.
ISSN
23146133
e-ISSN
23146141
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2552746705
Copyright
Copyright © 2021 Artur A. M. L. Brandt et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0/