Projets par an
Résumé
The CD2–CD58 protein–protein interaction is known to favor the recognition of antigen presenting cells by T cells. The structural, energetics, and dynamical properties of three known cyclic CD58 ligands, named P6, P7, and RTD-c, are studied through molecular dynamics (MD) simulations and molecular docking calculations. The ligands are built so as to mimic the C and F β-strands of protein CD2, connected via turn inducers. The MD analyses focus on the location of the ligands with respect to the experimental binding site and on the direct and water-mediated hydrogen bonds (H bonds) they form with CD58. Ligand P6, with a sequence close to the experimental β-strands of CD2, presents characteristics that explain its higher experimental affinity, e.g., the lower mobility and flexibility at the CD58 surface, and the larger number and occurrence frequency of ligand-CD58 H bonds. For the two other ligands, the structural modifications lead to changes in the binding pattern with CD58 and its dynamics. In parallel, a large set of molecular docking calculations, carried out with various search spaces and docking algorithms, are compared to provide a consensus view of the preferred ligand binding modes. The analysis of the ligand side chain locations yields results that are consistent with the CD2–CD58 crystal structure and suggests various binding modes of the experimentally identified hot spot of the ligands, i.e., Tyr86. P6 is shown to form a number of contacts that are also present in the experimental CD2–CD58 structure.
langue originale | Anglais |
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Pages (de - à) | 1295-1313 |
Nombre de pages | 19 |
journal | Journal of computer-aided molecular design |
Volume | 32 |
Numéro de publication | 11 |
Les DOIs | |
Etat de la publication | Publié - 1 nov. 2018 |
Empreinte digitale Examiner les sujets de recherche de « Investigating Cyclic Peptides Inhibiting CD2-CD58 Interactions through Molecular Dynamics and Molecular Docking Methods ». Ensemble, ils forment une empreinte digitale unique.
Projets
- 1 Terminé
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DoIFAD: Design Of peptide Inhibitors Fighting Autoimmune Disease
LEHERTE, L., Laurent, A. D., Vercauteren, D. & Jacquemin, D.
1/01/18 → 31/12/19
Projet: Recherche
Équipement
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Plateforme Technologique Calcul Intensif
Benoît Champagne (!!Manager)
Plateforme technologique Calcul intensifEquipement/installations: Plateforme technolgique
Activités
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Adèle Laurent
Laurence Leherte (Hôte)
7 oct. 2019 → 9 oct. 2019Activité: Types d'Accueil d'un visiteur › Accueil d'un chercheur étranger
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Neha Tripathi
Laurence Leherte (Hôte)
7 oct. 2019 → 9 oct. 2019Activité: Types d'Accueil d'un visiteur › Accueil d'un chercheur étranger
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Molecular dynamics simulations of cyclic ligand models interacting with protein CD58
Laurence Leherte (Orateur invité)
24 mai 2019Activité: Types de discours ou de présentation › Discours invité