| _version_ | 1866901949968809984 |
|---|---|
| author | Mahapatra, Subhasmita Sinha, Suman |
| author_facet | Mahapatra, Subhasmita Sinha, Suman |
| contents | <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> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19064170 |
| institution | Zenodo |
| language | |
| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Deciphering Glycan–Lectin Recognition Mechanisms Through Enhanced Sampling Simulations Mahapatra, Subhasmita Sinha, Suman Galectin-3, Glycan, GaMD, Allostery <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> |
| title | Deciphering Glycan–Lectin Recognition Mechanisms Through Enhanced Sampling Simulations |
| topic | Galectin-3, Glycan, GaMD, Allostery |
| url | https://doi.org/10.5281/zenodo.19064170 |