Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long Glycosaminoglycans
Glycosaminoglycans (GAGs) are linear anionic periodic polysaccharides participating in a number of biologically relevant processes in the extracellular matrix via interactions with their protein targets. Due to their periodicity, conformational flexibility, pseudo-symmetry of the sulfation pattern,...
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MDPI AG
2021-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/9/1349 |
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| author | Mateusz Marcisz Martyna Maszota-Zieleniak Bertrand Huard Sergey A. Samsonov |
| author_facet | Mateusz Marcisz Martyna Maszota-Zieleniak Bertrand Huard Sergey A. Samsonov |
| author_sort | Mateusz Marcisz |
| collection | DOAJ |
| description | Glycosaminoglycans (GAGs) are linear anionic periodic polysaccharides participating in a number of biologically relevant processes in the extracellular matrix via interactions with their protein targets. Due to their periodicity, conformational flexibility, pseudo-symmetry of the sulfation pattern, and the key role of electrostatics, these molecules are challenging for both experimental and theoretical approaches. In particular, conventional molecular docking applied for GAGs longer than 10-mer experiences severe difficulties. In this work, for the first time, 24- and 48-meric GAGs were docked using all-atomic repulsive-scaling Hamiltonian replica exchange molecular dynamics (RS-REMD), a novel methodology based on replicas with van der Waals radii of interacting molecules being scaled. This approach performed well for proteins complexed with oligomeric GAGs and is independent of their length, which distinguishes it from other molecular docking approaches. We built a model of long GAGs in complex with a proliferation-inducing ligand (APRIL) prebound to its receptors, the B cell maturation antigen and the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Furthermore, the prediction power of the RS-REMD for this tertiary complex was evaluated. We conclude that the TACI–GAG interaction could be potentially amplified by TACI’s binding to APRIL. RS-REMD outperformed Autodock3, the docking program previously proven the best for short GAGs. |
| first_indexed | 2024-03-10T07:52:32Z |
| format | Article |
| id | doaj.art-ad45b1c1699e48ae92d854c52950e455 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T07:52:32Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-ad45b1c1699e48ae92d854c52950e4552023-11-22T12:11:21ZengMDPI AGBiomolecules2218-273X2021-09-01119134910.3390/biom11091349Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long GlycosaminoglycansMateusz Marcisz0Martyna Maszota-Zieleniak1Bertrand Huard2Sergey A. Samsonov3Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, PolandFaculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, PolandLaboratory TIMC-IMAG, University Grenoble-Alpes, CNRS UMR 5525, 38700 La Tronche, FranceFaculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, PolandGlycosaminoglycans (GAGs) are linear anionic periodic polysaccharides participating in a number of biologically relevant processes in the extracellular matrix via interactions with their protein targets. Due to their periodicity, conformational flexibility, pseudo-symmetry of the sulfation pattern, and the key role of electrostatics, these molecules are challenging for both experimental and theoretical approaches. In particular, conventional molecular docking applied for GAGs longer than 10-mer experiences severe difficulties. In this work, for the first time, 24- and 48-meric GAGs were docked using all-atomic repulsive-scaling Hamiltonian replica exchange molecular dynamics (RS-REMD), a novel methodology based on replicas with van der Waals radii of interacting molecules being scaled. This approach performed well for proteins complexed with oligomeric GAGs and is independent of their length, which distinguishes it from other molecular docking approaches. We built a model of long GAGs in complex with a proliferation-inducing ligand (APRIL) prebound to its receptors, the B cell maturation antigen and the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Furthermore, the prediction power of the RS-REMD for this tertiary complex was evaluated. We conclude that the TACI–GAG interaction could be potentially amplified by TACI’s binding to APRIL. RS-REMD outperformed Autodock3, the docking program previously proven the best for short GAGs.https://www.mdpi.com/2218-273X/11/9/1349van der Waals replica exchange molecular dynamicslong glycosaminoglycansAPRILAPRIL receptorsMM/GBSA |
| spellingShingle | Mateusz Marcisz Martyna Maszota-Zieleniak Bertrand Huard Sergey A. Samsonov Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long Glycosaminoglycans Biomolecules van der Waals replica exchange molecular dynamics long glycosaminoglycans APRIL APRIL receptors MM/GBSA |
| title | Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long Glycosaminoglycans |
| title_full | Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long Glycosaminoglycans |
| title_fullStr | Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long Glycosaminoglycans |
| title_full_unstemmed | Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long Glycosaminoglycans |
| title_short | Advanced Molecular Dynamics Approaches to Model a Tertiary Complex APRIL/TACI with Long Glycosaminoglycans |
| title_sort | advanced molecular dynamics approaches to model a tertiary complex april taci with long glycosaminoglycans |
| topic | van der Waals replica exchange molecular dynamics long glycosaminoglycans APRIL APRIL receptors MM/GBSA |
| url | https://www.mdpi.com/2218-273X/11/9/1349 |
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