Computational Interactions between the Endohedral Metallofullerene Gd@C60 and Human Toll-Like Receptor 3: A Molecular Docking and Molecular Dynamics Study
Abstract
Background: Endohedral metallofullerenes (EMFs), such as the gadolinium fullerene Gd@C60, are being explored as kinetically stable alternatives to gadolinium chelate contrast agents and as platforms for nanomedicine. Their behavior in a biological medium depends strongly on how they interact with proteins. Toll-like receptor 3 (TLR3) is an endosomal receptor that senses double-stranded RNA, and it is a relevant partner because nanoparticles are commonly internalized into endosomes. How Gd@C60 might bind to human TLR3 (hTLR3) is not known. Methods: A Gd@C60 model was built by inserting Gd3+ into C60 and optimized with the universal force field. It was docked to the crystal structure of the hTLR3 ectodomain (PDB ID: 1ZIW) using the PatchDock shape-complementarity algorithm. The top-ranked complex was then simulated for 20 ns in explicit solvent (TIP3P water, 0.15 mol/L KCl) with NAMD 2.13 and the CHARMM36 force field. Results: The best-ranked docking solution (geometric complementarity score 3908) placed Gd@C60 in the C-terminal cap region of the horseshoe-shaped receptor. The pose is stabilized by π–π stacking with Trp656, electrostatic interactions with Lys627 and Arg635, and a hydrophobic contact with Ile654, all without covalent bonding. In the simulation, the receptor backbone RMSD fluctuated at about 3–5 Å, whereas the fullerene RMSD fluctuated more widely with intermittent spikes. Conclusions: Aromatic, electrostatic and hydrophobic contacts together define the predicted binding mode of Gd@C60 on hTLR3. The net charge on the cage complicates the identification of a suitable binding pocket. The results provide a starting point for quantum-mechanical and free-energy studies and for the design of nanomaterial-based sensors of nucleic acids.
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BibTeX
@misc{kaliamurthi2026computational,
title = {{Computational Interactions between the Endohedral Metallofullerene Gd@C60 and Human Toll-Like Receptor 3: A Molecular Docking and Molecular Dynamics Study}},
author = {Satyavani Kaliamurthi and Gurudeeban Selvaraj and Gilles H. Peslherbe and Dong-qing Wei},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010999/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010999/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Computational Interactions between the Endohedral Metallofullerene Gd@C60 and Human Toll-Like Receptor 3: A Molecular Docking and Molecular Dynamics Study
AU - Satyavani Kaliamurthi
AU - Gurudeeban Selvaraj
AU - Gilles H. Peslherbe
AU - Dong-qing Wei
PY - 2026
DA - 2026/10/25
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010999/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010999/v1
AB - Background: Endohedral metallofullerenes (EMFs), such as the gadolinium fullerene Gd@C60, are being explored as kinetically stable alternatives to gadolinium chelate contrast agents and as platforms for nanomedicine. Their behavior in a biological medium depends strongly on how they interact with proteins. Toll-like receptor 3 (TLR3) is an endosomal receptor that senses double-stranded RNA, and it is a relevant partner because nanoparticles are commonly internalized into endosomes. How Gd@C60 might bind to human TLR3 (hTLR3) is not known. Methods: A Gd@C60 model was built by inserting Gd3+ into C60 and optimized with the universal force field. It was docked to the crystal structure of the hTLR3 ectodomain (PDB ID: 1ZIW) using the PatchDock shape-complementarity algorithm. The top-ranked complex was then simulated for 20 ns in explicit solvent (TIP3P water, 0.15 mol/L KCl) with NAMD 2.13 and the CHARMM36 force field. Results: The best-ranked docking solution (geometric complementarity score 3908) placed Gd@C60 in the C-terminal cap region of the horseshoe-shaped receptor. The pose is stabilized by π–π stacking with Trp656, electrostatic interactions with Lys627 and Arg635, and a hydrophobic contact with Ile654, all without covalent bonding. In the simulation, the receptor backbone RMSD fluctuated at about 3–5 Å, whereas the fullerene RMSD fluctuated more widely with intermittent spikes. Conclusions: Aromatic, electrostatic and hydrophobic contacts together define the predicted binding mode of Gd@C60 on hTLR3. The net charge on the cage complicates the identification of a suitable binding pocket. The results provide a starting point for quantum-mechanical and free-energy studies and for the design of nanomaterial-based sensors of nucleic acids.
ER -