| Autor: |
Jino Blessy J; Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India., Siva Shanmugam NR; Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India., Veluraja K; PSN college of Engineering and Technology, Tirunelveli, Tamilnadu, India., Michael Gromiha M; Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2022; Vol. 40 (20), pp. 10094-10105. Date of Electronic Publication: 2021 Jul 05. |
| DOI: |
10.1080/07391102.2021.1939788 |
| Abstrakt: |
Galectin-1 (Gal-1) is the first member of galectin family, which has a carbohydrate recognition domain, specifically binds towards β -galactoside containing oligosaccharides. Owing its association with carbohydrates, Gal-1 is involved in many biological processes such as cell signaling, adhesion and pathological pathways such as metastasis, apoptosis and increased tumour cell survival. The development of β-galactoside based inhibitors would help to control the Gal-1 expression. In the current study, we carried out molecular dynamics (MD) simulations to examine the structural and dynamic behaviour Gal-1-thiodigalactoside (TDG), Gal-1-lactobionic acid (LBA) and Gal-1-beta-(1→6)-galactobiose (G16G) complexes. The analysis of glycosidic torsional angles revealed that β -galactoside analogues TDG and LBA have a single binding mode (BM1) whereas G16G has two binding modes (BM1 and BM2) for interacting with Gal-1 protein. We have computed the binding free energies for the complexes Gal-1-TDG, Gal-1-LBA and Gal-1-G16G using MM/PBSA and are -6.45, -6.22 and -3.08 kcal/mol, respectively. This trend agrees well with experiments that the binding of Gal-1 with TDG is stronger than LBA. Further analysis revealed that the interactions due to direct and water-mediated hydrogen bonds play a significant role to the structural stability of the complexes. The result obtained from this study is useful to formulate a set of rules and derive pharmacophore-based features for designing inhibitors against galectin-1.Communicated by Ramaswamy H. Sarma. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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