Molecular modeling study of immediate and delayed drugs hypersensitivities : β-lactams antibiotics allergenicity
type: Dataset
description: Drug hypersensitivity is an immune-mediated reaction to a drug. Our work was divided into four stages: 1 - We have classified β-lactam antibiotics based on their molecular fields, and obtained a dendrogram of 4 families, validated by clinical data. We also conducted a 3D-QSAR study to determine what parts of the drug are involved in the pathology and to predict the allergenicity of β- lactams. 2 - Under the assumption that β-lactam antibiotics are haptens, we studied their reactivity in comparison with lysine and serine. We then conducted "docking" experiments to define the interactions between the drug and human serum albumin. We conclude that lysine 190 and 212 are the most suitable sites for the covalent binding of the drugs. We validate this analysis by mixed QM / MM methods. Finally, thanks to our software SuMo, we have found other candidate proteins for haptenization. 3 - Regarding immediate hypersensitivity reactions, we modeled the IgE, the β-lactam and the haptenized protein. We considered several modes of recognition. Secondly, we analyzed the structural changes of the protein induced by the binding of the drug. 4 - Concerning delayed reactions, we considered different scenarios for the recognition of β-lactam by the TCR. We modeled complexes involving the TCR, the peptide haptenized by the β-lactam, a possible ion, and the MHC. We investigated them with molecular dynamics to study their relevance. On the other hand, we have identified many peptides derived from haptenization proteins and able to present the drug to the TCR through the MHC. The validity of the obtained results is or will be confirmed using experiments in vitro and in vivo.
identifier: NNT: 2010LYO10318
issued: 2026-05-09T19:31:12.683182
language: fr
modified: 2026-05-09T19:31:12.683186
contact point: Organization
  fn: CCSD
keyword: -lactam
keyword: -lactamine
keyword: albumin
keyword: albumine
keyword: cmh
keyword: docking
keyword: drug-hypersensitivity
keyword: dynamique-moleculaire
keyword: hypersensibilite-allergique
keyword: ige
keyword: infoeu-reposemanticsdoctoralthesis
keyword: mecanique-quantique--moleculaire
keyword: mhc
keyword: molecular-dynamics
keyword: reactivite
keyword: reactivity
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: sumo
keyword: tcr
keyword: theses
landing page: https://theses.hal.science/tel-00860118

Molecular modeling study of immediate and delayed drugs hypersensitivities : β-lactams antibiotics allergenicity
type: Distribution
format: HTML
issued: 2026-05-09T19:31:12.685182
modified: 2026-05-09T19:31:12.660987
access URL: https://theses.hal.science/tel-00860118

test_moissonnage_selune
type: Agent