Molecular dynamics simulation, free energy landscape and binding free energy computations in exploration the anti-invasive activity of amygdalin against metastasis

Al-Khafaji, Khattab; Tok, Tuğba Taşkın

doi:10.1016/j.cmpb.2020.105660

Cited by 66 publications

(37 citation statements)

References 55 publications

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“…Following the superposition of core residues, PCA was performed to examine the conformers based on their equivalent residues. The PCs collected during MD simulation are originally the eigenvector values collected from the covariance matrix, each corresponding to the change in protein trajectory ( Al-Khafaji and Taskin Tok, 2020 ). In order to obtain a lower-dimensional representation of the structural dataset, we project the distribution onto the subspace defined by the largest principal components.…”

Section: Methodsmentioning

confidence: 99%

Targeting N-Terminal Human Maltase-Glucoamylase to Unravel Possible Inhibitors Using Molecular Docking, Molecular Dynamics Simulations, and Adaptive Steered Molecular Dynamics Simulations

et al. 2021

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There are multiple drugs for the treatment of type 2 diabetes, including traditional sulfonylureas biguanides, glinides, thiazolidinediones, α-glucosidase inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT2) inhibitors. α-Glucosidase inhibitors have been used to control postprandial glucose levels caused by type 2 diabetes since 1990. α-Glucosidases are rather crucial in the human metabolic system and are principally found in families 13 and 31. Maltase-glucoamylase (MGAM) belongs to glycoside hydrolase family 31. The main function of MGAM is to digest terminal starch products left after the enzymatic action of α-amylase; hence, MGAM becomes an efficient drug target for insulin resistance. In order to explore the conformational changes in the active pocket and unbinding pathway for NtMGAM, molecular dynamics (MD) simulations and adaptive steered molecular dynamics (ASMD) simulations were performed for two NtMGAM-inhibitor [de-O-sulfonated kotalanol (DSK) and acarbose] complexes. MD simulations indicated that DSK bound to NtMGAM may influence two domains (inserted loop 1 and inserted loop 2) by interfering with the spiralization of residue 497–499. The flexibility of inserted loop 1 and inserted loop 2 can influence the volume of the active pocket of NtMGAM, which can affect the binding progress for DSK to NtMGAM. ASMD simulations showed that compared to acarbose, DSK escaped from NtMGAM easily with lower energy. Asp542 is an important residue on the bottleneck of the active pocket of NtMGAM and could generate hydrogen bonds with DSK continuously. Our theoretical results may provide some useful clues for designing new α-glucosidase inhibitors to treat type 2 diabetes.

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Section: Methodsmentioning

confidence: 99%

Targeting N-Terminal Human Maltase-Glucoamylase to Unravel Possible Inhibitors Using Molecular Docking, Molecular Dynamics Simulations, and Adaptive Steered Molecular Dynamics Simulations

et al. 2021

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“…PatchDock represents the Connolly's surface of docking as flat, convex, and concave patches and conforms BioMed Research International them to produce candidate transformations [41]. For each aptamer-protein complex, we extracted two select cluster with higher score for using as the initial set of coordinates in the MD simulations [42][43][44].…”

Section: Molecular Dockingmentioning

confidence: 99%

[Retracted] Atomic Scale Interactions between RNA and DNA Aptamers with the TNF‐α Protein

Asadzadeh

Moosavi

Alexandrakis

et al. 2021

BioMed Research International

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Interest in the design and manufacture of RNA and DNA aptamers as apta-biosensors for the early diagnosis of blood infections and other inflammatory conditions has increased considerably in recent years. The practical utility of these aptamers depends on the detailed knowledge about the putative interactions with their target proteins. Therefore, understanding the aptamer-protein interactions at the atomic scale can offer significant insights into the optimal apta-biosensor design. In this study, we consider one RNA and one DNA aptamer that were previously used as apta-biosensors for detecting the infection biomarker protein TNF-α, as an example of a novel computational workflow for selecting the aptamer candidate with the highest binding strength to a target. We combine information from the binding free energy calculations, molecular docking, and molecular dynamics simulations to investigate the interactions of both aptamers with TNF-α. The results reveal that the RNA aptamer has a more stable structure relative to the DNA aptamer. Interaction of aptamers with TNF-α does not have any negative effect on its structure. The results of molecular docking and molecular dynamics simulations suggest that the RNA aptamer has a stronger interaction with the protein. Also, these findings illustrate that basic residues of TNF-α establish more atomic contacts with the aptamers compared to acidic or pH-neutral ones. Furthermore, binding energy calculations show that the interaction of the RNA aptamer with TNF-α is thermodynamically more favorable. In total, the findings of this study indicate that the RNA aptamer is a more suitable candidate for using as an apta-biosensor of TNF-α and, therefore, of greater potential use for the diagnosis of blood infections. Also, this study provides more information about aptamer-protein interactions and increases our understanding of this phenomenon.

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“…Docking results determine the measure of ligand interaction with the active site of the targeted protein. The active sites are the coordinates of the ligand in the original target protein grids [ 114 ] through PyMol and Drug Discovery Studio version 4.5 is used for scrutinizing these active binding sites of the target protein [ 115 ].…”

Section: Methodsmentioning

confidence: 99%

“…The active sites are the coordinates of the ligand in the original target protein grids [114] through PyMol and Drug Discovery Studio version 4.5 is used for scrutinizing these active binding sites of the target protein [115].…”

Section: Docking Protocolmentioning

confidence: 99%

Quercetin and/or Ascorbic Acid Modulatory Effect on Phenobarbital-Induced Sleeping Mice Possibly through GABAA and GABAB Receptor Interaction Pathway

et al. 2021

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Background: Depressive disorder is a recurrent illness that affects large numbers of the general population worldwide. In recent years, the goal of depression treatment has moved from symptomatic response to that of full remission. However, treatment-resistant depression is a major challenge in the treatment of depression or depression-related disorders. Consensus opinion, therefore, suggests that effective combined aggressive initial treatment is the most appropriate strategy. Objectives: This study aimed to evaluate the effects of quercetin (QUR) and/or ascorbic acid (AA) on Phenobarbital-induced sleeping mice. Methods: QUR (50 mg/kg) and/or AA (25 mg/kg) with or without intraperitoneally pre-treated with GABA receptor agonist (diazepam: 2 mg/kg, i.p.) or antagonist (Flumazenil: 2.5 mg/kg, i.p.) to underscore the effects, as well as the possible involvement of the GABA receptor in the modulatory action of QUR and AA in sleeping mice. Additionally, an in silico study was undertaken to predict the involvement of GABA receptors in the sleep mechanism. Results: Findings suggest that the pretreatment of QUR and AA modulated the onset and duration of action of the standard drugs in experimental animals. The acute administration of QUR and/or AA significantly (p < 0.05) reversed the DZP-mediated onset of action and slightly reversed the duration of sleep time in comparison to the vehicle (control) group. A further combination of QUR or AA with the FLU resulted in an enhancement of the onset of action while reducing the duration of action, suggesting a FLU-like effect on the test animals. In in silico studies, AA and QUR showed good to moderate binding affinities with GABAA and GABAB receptors. Conclusions: Both QUR and AA produced a stimulatory-like effect on mice, possibly through the GABAA and GABAB receptor interaction pathways. Further studies are necessary to verify this activity and clarify the exact mechanism of action(s) involved.

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Molecular dynamics simulation, free energy landscape and binding free energy computations in exploration the anti-invasive activity of amygdalin against metastasis

Cited by 66 publications

References 55 publications

Targeting N-Terminal Human Maltase-Glucoamylase to Unravel Possible Inhibitors Using Molecular Docking, Molecular Dynamics Simulations, and Adaptive Steered Molecular Dynamics Simulations

Targeting N-Terminal Human Maltase-Glucoamylase to Unravel Possible Inhibitors Using Molecular Docking, Molecular Dynamics Simulations, and Adaptive Steered Molecular Dynamics Simulations

[Retracted] Atomic Scale Interactions between RNA and DNA Aptamers with the TNF‐α Protein

Quercetin and/or Ascorbic Acid Modulatory Effect on Phenobarbital-Induced Sleeping Mice Possibly through GABAA and GABAB Receptor Interaction Pathway

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