Modeling glycosaminoglycan–protein complexes

Kogut, Małgorzata M.; Marcisz, Mateusz; Samsonov, Sergey A.

doi:10.1016/j.sbi.2022.102332

Cited by 20 publications

(19 citation statements)

References 61 publications

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“…When applied to GAG–protein complexes, computational approaches aim to characterize the molecular nature of the interactions ( e.g. , the noncovalent bonds, the GAG chemical groups, and the amino acids involved), their mechanism of action, the role of basic domain motions, and the influence of possible mutations. , …”

Section: Protein-glycosaminoglycan Interactionsmentioning

confidence: 99%

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Glycosaminoglycans: What Remains To Be Deciphered?

Pérez

Makshakova

Angulo

et al. 2023

JACS Au

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Glycosaminoglycans (GAGs) are complex polysaccharides exhibiting a vast structural diversity and fulfilling various functions mediated by thousands of interactions in the extracellular matrix, at the cell surface, and within the cells where they have been detected in the nucleus. It is known that the chemical groups attached to GAGs and GAG conformations comprise “glycocodes” that are not yet fully deciphered. The molecular context also matters for GAG structures and functions, and the influence of the structure and functions of the proteoglycan core proteins on sulfated GAGs and vice versa warrants further investigation. The lack of dedicated bioinformatic tools for mining GAG data sets contributes to a partial characterization of the structural and functional landscape and interactions of GAGs. These pending issues will benefit from the development of new approaches reviewed here, namely (i) the synthesis of GAG oligosaccharides to build large and diverse GAG libraries, (ii) GAG analysis and sequencing by mass spectrometry (e.g., ion mobility-mass spectrometry), gas-phase infrared spectroscopy, recognition tunnelling nanopores, and molecular modeling to identify bioactive GAG sequences, biophysical methods to investigate binding interfaces, and to expand our knowledge and understanding of glycocodes governing GAG molecular recognition, and (iii) artificial intelligence for in-depth investigation of GAGomic data sets and their integration with proteomics.

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Section: Protein-glycosaminoglycan Interactionsmentioning

confidence: 99%

“…, the noncovalent bonds, the GAG chemical groups, and the amino acids involved), their mechanism of action, the role of basic domain motions, and the influence of possible mutations. 121 , 122 …”

Section: Protein-glycosaminoglycan Interactionsmentioning

confidence: 99%

Glycosaminoglycans: What Remains To Be Deciphered?

Pérez

Makshakova

Angulo

et al. 2023

JACS Au

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“…As such, heparan sulfates and heparins have been found to interact with growth factors and cell surface receptors, promoting the formation of signaling transduction [ 25 , 26 ]. Furthermore, heparan sulfate and heparin chains also interact with proteins to regulate overall integrity and stability through large protein assemblies [ 27 , 28 , 29 ]. Over 2800 heparan sulfate binding proteins have been identified as part of the human interactome to date [ 9 ].…”

Section: The Role Of Heparan Sulfates In Cellular Signaling and Organ...mentioning

confidence: 99%

Heparin Mimetics and Their Impact on Extracellular Matrix Protein Assemblies

2023

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Heparan sulfate is a crucial extracellular matrix component that organizes structural features and functional protein processes. This occurs through the formation of protein–heparan sulfate assemblies around cell surfaces, which allow for the deliberate local and temporal control of cellular signaling. As such, heparin-mimicking drugs can directly affect these processes by competing with naturally occurring heparan sulfate and heparin chains that then disturb protein assemblies and decrease regulatory capacities. The high number of heparan-sulfate-binding proteins that are present in the extracellular matrix can cause obscure pathological effects that should be considered and examined in more detail, especially when developing novel mimetics for clinical use. The objective of this article is to investigate recent studies that present heparan-sulfate-mediated protein assemblies and the impact of heparin mimetics on the assembly and function of these protein complexes.

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“…Furthermore, GAGs display high flexibility, periodicity and a particular property that is termed multipose binding. 47 This means that they can bind multiple sites on the protein surface and/or in multiple poses in one binding region (e.g., at different angles between the GAG chains in those poses). This phenomenon, depending on the range of flexibility and conformational freedom of the GAG upon binding to the protein, may be also called either plastic or non-selective binding.…”

Section: Rs-remd Docking Performancementioning

confidence: 99%

Explicit solvent repulsive scaling replica exchange molecular dynamics (RS‐REMD) in molecular modeling of protein‐glycosaminoglycan complexes

et al. 2022

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Glycosaminoglcyans (GAGs), linear anionic periodic polysaccharides, are crucial for many biologically relevant functions in the extracellular matrix. By interacting with proteins GAGs mediate processes such as cancer development, cell proliferation and the onset of neurodegenerative diseases. Despite this eminent importance of GAGs, they still represent a limited focus for the computational community in comparison to other classes of biomolecules. Therefore, there is a lack of modeling tools designed specifically for docking GAGs. One has to rely on existing docking software developed mostly for small drug molecules substantially differing from GAGs in their basic physico-chemical properties. In this study, we present an updated protocol for docking GAGs based on the Repulsive Scaling Replica Exchange Molecular Dynamics (RS-REMD) that includes explicit solvent description. The use of this water model improved docking performance both in terms of its accuracy and speed. This method represents a significant computational progress in GAG-related research.

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Modeling glycosaminoglycan–protein complexes

Cited by 20 publications

References 61 publications

Glycosaminoglycans: What Remains To Be Deciphered?

Glycosaminoglycans: What Remains To Be Deciphered?

Heparin Mimetics and Their Impact on Extracellular Matrix Protein Assemblies

Explicit solvent repulsive scaling replica exchange molecular dynamics (RS‐REMD) in molecular modeling of protein‐glycosaminoglycan complexes

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