| Author | Chaves, Beatriz | |
| Author | Sartori, Geraldo R. | |
| Author | Vasconcelos, Disraeli C. A. | |
| Author | Savino, Wilson | |
| Author | Caffarena, Ernesto R. | |
| Author | Almeida, Vinicius Cotta de | |
| Author | Silva, João H. M. da | |
| Access date | 2021-01-09T18:35:18Z | |
| Available date | 2021-01-09T18:35:18Z | |
| Document date | 2020 | |
| Citation | CHAVES, Beatriz et al. Guidelines To Predict Binding Poses of Antibody−Integrin Complexes. ACS Omega, v. 5, p. 16379-16385, June 2020. | pt_BR |
| ISSN | 2470-1343 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/45545 | |
| Language | eng | pt_BR |
| Publisher | American Chemical Society | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Diretrizes | pt_BR |
| Subject in Portuguese | Anticorpos-integrin Complexos | pt_BR |
| Subject in Portuguese | Prever poses de vinculação | pt_BR |
| Title | Guidelines To Predict Binding Poses of Antibody−Integrin Complexes | pt_BR |
| Type | Article | |
| DOI | 10.1021/acsomega.0c00226 | |
| Abstract | Integrins are cell adhesion receptors that transmit
bidirectional signals across the plasma membrane. They are
noncovalently linked heterodimeric molecules consisting of two
subunits and act as biomarkers in several pathologies. Thus,
according to the increase of therapeutic antibody production, some
efforts have been applied to produce anti-integrin antibodies. Here,
we purposed to evaluate methods of generation and identification of
the binding pose of integrin−antibody complexes, through protein−
protein docking and molecular dynamics simulations, and propose a
strategy to assure the confidence of the final model and avoid falsepositive
poses. The results show that ClusPro and GRAMM-X were
the best programs to generate the native pose of integrin−antibody
complexes. Furthermore, we were able to recover and to ensure that
the selected pose is the native one by using a simple rule. All
complexes from ClusPro in which the first model had the lowest energy, at least 5% more negative than the second one, were
correctly predicted. Therefore, our methodology seems to be efficient to avoid misranking of wrong poses for integrin−antibody
complexes. In cases where the rule is inconclusive, we proposed the use of heated molecular dynamics to identify the native pose
characterized by RMSDi <0.5 nm. We believe that the set of methods presented here helps in the rational design of anti-integrin
antibodies, giving some insights on the development of new biopharmaceuticals. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Fiocruz Ceará. Grupo de Modelagem Computacional. Eusébio, CE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Fiocruz Ceará. Grupo de Modelagem Computacional. Eusébio, CE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Fiocruz Ceará. Grupo de Modelagem Computacional. Eusébio, CE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Grupo de Modelagem Molecular e Biofísica Computacional. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Fiocruz Ceará. Grupo de Modelagem Computacional. Eusébio, CE, Brasil. | pt_BR |
| Subject | Guidelines | pt_BR |
| Subject | Predict Binding Poses | pt_BR |
| Subject | Antibody−Integrin Complexes | pt_BR |
