Computational insights into the role of calcium ions in protein–glycosaminoglycan systems

Kogut, Małgorzata M.; Maszota‐Zieleniak, Martyna; Marcisz, Mateusz; Samsonov, Sergey A.

doi:10.1039/d0cp05438k

Cited by 15 publications

(14 citation statements)

References 64 publications

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“…29,30 GAGs can influence the cell signaling and the activity of the proteins by changing their conformation or by oligomerization facilitation of their receptors by binding and clustering multiple fibroblast growth factors (FGFs) simultaneously. 31,32 In the context of the protein−GAG interaction, several computational approaches, like docking and molecular dynamics (MD) simulations, were used to predict the binding sites on the protein 33−36 and the interaction of GAGs with several proteins like VEGF, 25 IL10, 34,37,38 acidic fibroblast growth factor, 26 protein−ion−GAG complexes, 39 etc.…”

Section: ■ Introductionmentioning

confidence: 99%

Effect of Sulfation on the Conformational Dynamics of Dermatan Sulfate Glycosaminoglycan: A Gaussian Accelerated Molecular Dynamics Study

2022

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Glycosaminoglycans (GAGs) are anionic biopolymers present on cell surfaces as a part of proteoglycans. The biological activities of GAGs depend on the sulfation pattern. In our study, we have considered three octadecasaccharide dermatan sulfate (DS) chains with increasing order of sulfation ( dp 6s, dp 7s, and dp 12s) to illuminate the role of sulfation on the GAG units and its chain conformation through 10 μs-long Gaussian accelerated molecular dynamics simulations. DS is composed of repeating disaccharide units of iduronic acid (IdoA) and N-acetylgalactosamine (N-GalNAc). Here, N-GalNAc is linked to IdoA via β(1–4), while IdoA is linked to N-GalNAc through α(1–3). With the increase in sulfation, the DS structure becomes more rigid and linear, as is evident from the distribution of root-mean-square deviations (RMSDs) and end-to-end distances. The tetrasaccharide linker region of the main chain shows a rigid conformation in terms of the glycosidic linkage. We have observed that upon sulfation (i.e., dp 12s), the ring flip between two chair forms vanished for IdoA. The dynamic cross-correlation analysis reveals that the anticorrelation motions in dp 12s are reduced significantly compared to dp 6s or dp 7s. An increase in sulfation generates relatively more stable hydrogen-bond networks, including water bridging with the neighboring monosaccharides. Despite the favorable linear structures of the GAG chains, our study also predicts few significant bendings related to the different puckering states, which may play a notable role in the function of the DS. The relation between the global conformation with the micro-level parameters such as puckering and water-mediated hydrogen bonds shapes the overall conformational space of GAGs. Overall, atomistic details of the DS chain provided in this study will help understand their functional and mechanical roles, besides developing new biomaterials.

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Section: ■ Introductionmentioning

confidence: 99%

Effect of Sulfation on the Conformational Dynamics of Dermatan Sulfate Glycosaminoglycan: A Gaussian Accelerated Molecular Dynamics Study

2022

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“…The selectivity of the binding poses was calculated using method proposed by Siebenmorgen et al . [42] and described in details in our previous work [43] . The only modification of this approach applied here consisted of considering best scored pose as a reference for “correct” docking results since there are no reference experimental structures available.…”

Section: Methodsmentioning

confidence: 99%

The potential role of glycosaminoglycans in serum amyloid A fibril formation by in silico approaches

Maszota‐Zieleniak

Danielsson

Samsonov

2021

Matrix Biology Plus

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Section: Introductionmentioning

confidence: 99%

“…Many computational studies on GAGs show their promising potential in the examination of the protein–GAG interactions. The following studies successfully investigated effects of the GAGs binding on a variety of different proteins, such as CXCL-14, VEGF, CXCL-8, ,, a Proliferation Inducing Ligand (APRIL), IL-10, ,, CXCL-12, acidic fibroblast growth factor (FGF-1), or protein–ion–GAG complexes …”

Section: Introductionmentioning

confidence: 99%

“…The following studies successfully investigated effects of the GAGs binding on a variety of different proteins, such as CXCL-14, 11 VEGF, 7 CXCL-8, 9,24,28 a Proliferation Inducing Ligand (APRIL), 29 IL-10, 25,26,30 CXCL-12, 31 acidic fibroblast growth factor (FGF-1), 32 or protein−ion−GAG complexes. 33 Even though computational studies seem to be very successful and helpful in protein−GAG investigations, there are still a lot of challenges that have not been fully overcome yet. One of them is docking long GAG molecules.…”

Section: ■ Introductionmentioning

confidence: 99%

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Modeling Protein–Glycosaminoglycan Complexes: Does the Size Matter?

Marcisz

Zacharias

Samsonov

2021

J. Chem. Inf. Model.

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Docking glycosaminoglycans (GAGs) has been challenging because of the complex nature of these long periodic linear and negatively charged polysaccharides. Although standard docking tools like Autodock3 are successful when docking GAGs up to hexameric length, they experience challenges to properly dock longer GAGs. Similar limitations concern other docking approaches typically developed for docking ligands of limited size to proteins. At the same time, most of more advanced docking approaches are challenging for a user who is inexperienced with complex in silico methodologies. In this work, we evaluate the binding energies of complexes with different lengths of GAGs using all-atom molecular dynamics simulations. Based on this analysis, we propose a new docking protocol for long GAGs that consists of conventional docking of short GAGs and further elongation with the use of a coarse-grained representation of the GAG parts not being in direct contact with its protein receptor. This method automated by a simple script is straightforward to use within the Autodock3 framework but also useful in combination with other standard docking tools. We believe that this method with some minor case-specific modifications could also be used for docking other linear charged polymers.

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Computational insights into the role of calcium ions in protein–glycosaminoglycan systems

Abstract: The prediction power of computational methodologies for studying the role of ions in protein–glycosaminoglycan interactions was critically assessed.

Cited by 15 publications

References 64 publications

Effect of Sulfation on the Conformational Dynamics of Dermatan Sulfate Glycosaminoglycan: A Gaussian Accelerated Molecular Dynamics Study

Effect of Sulfation on the Conformational Dynamics of Dermatan Sulfate Glycosaminoglycan: A Gaussian Accelerated Molecular Dynamics Study

The potential role of glycosaminoglycans in serum amyloid A fibril formation by in silico approaches

Modeling Protein–Glycosaminoglycan Complexes: Does the Size Matter?

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