Projects per year
Abstract
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.
Original language | English |
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Pages (from-to) | 1295-1313 |
Number of pages | 19 |
Journal | Journal of computer-aided molecular design |
Volume | 32 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Nov 2018 |
Keywords
- CD58
- cyclic peptides
- ligands
- molecular docking
- molecular dynamics
- inhibitor
- Cyclic peptides
- Molecular dynamics
- Ligands
- Inhibitor
- Molecular docking
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Projects
- 1 Finished
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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
Project: Research
Equipment
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High Performance Computing Technology Platform
Benoît Champagne (Manager)
Technological Platform High Performance ComputingFacility/equipment: Technological Platform
Activities
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Adèle Laurent
Laurence Leherte (Host)
7 Oct 2019 → 9 Oct 2019Activity: Hosting a visitor types › Hosting a researcher
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Neha Tripathi
Laurence Leherte (Host)
7 Oct 2019 → 9 Oct 2019Activity: Hosting a visitor types › Hosting a researcher
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Molecular dynamics simulations of cyclic ligand models interacting with protein CD58
Laurence Leherte (Invited speaker)
24 May 2019Activity: Talk or presentation types › Invited talk