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| Auteurs principaux: | , |
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| Format: | Recurso digital |
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Zenodo
2026
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| Accès en ligne: | https://doi.org/10.5281/zenodo.19064170 |
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- <p>Galectin-3 is a β-galactoside-binding protein involved in multiple biological processes,<br>including cell proliferation, apoptosis, and inflammatory response. The pivotal role played by<br>galectin-3 in diverse cellular processes makes it a therapeutic target of choice against cancers.<br>However, the dynamic interplay of galectin-3 with diverse carbohydrate ligands is yet to be<br>fully understood in detail. Elucidating molecular recognition mechanism(s) of ligand binding<br>in a system such as galectin-3 is crucial for biological function and has promising<br>implications in drug discovery. However, capturing these rare-event mechanisms using<br>atomistic molecular dynamics simulations is a computationally expensive task. Our work<br>aims to uncover the nuances of one such crucial mechanism using Gaussian accelerated<br>molecular dynamics (GaMD) with galectin-3 as a prototypical system. The current work<br>employs GaMD to explore the intricate binding mechanisms of galectin-3 with glycans of<br>varying chain lengths. Our results show that pentasaccharides and ortho-fluoro derivatives as<br>longer-chain glycans have interacted with galectin-3 strongly and stably, recapitulating the<br>co-crystal pose. These ligands interact not only with CRD of galectin-3 but remain bound in<br>the native pocket over longer timescales, in contrast to shorter-chain ligands such as beta-<br>lactose and TF-antigen. However, due to inherent conformational flexibility, shorter-chain<br>ligands were observed to sample allosteric pockets prior to reaching the native binding mode.<br>This suggests that the length of the galectin-3 ligand plays a crucial role in determining its<br>mode of interaction. This study advances the understanding of galectin-3 recognition and<br>provides important considerations for designing effective galectin-3-targeting therapeutics.</p>