| Author | Brandt, Artur A. M. I.. | |
| Author | Silva, Rodrigo N. Rodrigues da | |
| Author | Lima Junior, Josué C. | |
| Author | Alves, Carlos R. | |
| Author | Silva, Franklin de Souza | |
| Access date | 2021-07-14T14:23:52Z | |
| Available date | 2021-07-14T14:23:52Z | |
| Document date | 2021 | |
| Citation | BRADNT, Artur A. M. L. et al. Combining Well-Tempered Metadynamics Simulation and SPR Assays to Characterize the Binding Mechanism of the Universal T Lymphocyte Tetanus Toxin Epitope TT830-843. BioMed Research International, v 2021, Article 5568980, 15 p, July 2021. | pt_BR |
| ISSN | 2314-6133 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/48234 | |
| Language | eng | pt_BR |
| Publisher | Hindawi | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Simulação de Metadinâmica Bem Temperada | pt_BR |
| Subject in Portuguese | SPR Ensaios | pt_BR |
| Subject in Portuguese | Mecanismo de ligação | pt_BR |
| Subject in Portuguese | Epítopo da toxina | pt_BR |
| Subject in Portuguese | Llinfócito T universal TT830-843 | pt_BR |
| Subject in Portuguese | Tétano | pt_BR |
| Title | Combining Well-Tempered Metadynamics Simulation and SPR Assays to Characterize the Binding Mechanism of the Universal T Lymphocyte Tetanus Toxin Epitope TT830-84 | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1155/2021/5568980 | |
| 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. | pt_BR |
| Affilliation | Faculdade de Educação Tecnológica do Estado do Rio de Janeiro. Rio de Janeiro, RJ, Brasil / Univeritas-Rio. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Laboratório de Tecnologia Diagnóstica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Universidade Iguaçu. Faculdade de Ciências Biológicas e da Saúde. Nova Iguaçu, RJ, Brasil. | pt_BR |
| Subject | Well-Tempered Metadynamics Simulation | pt_BR |
| Subject | SPR Assays | pt_BR |
| Subject | Binding Mechanism | pt_BR |
| Subject | Toxin Epitope TT830-843 | pt_BR |
| Subject | Universal T Lymphocyte Tetanus | pt_BR |
