Visual dynamics: a WEB application for molecular dynamics simulation using GROMACS

Vieira, Ivo Henrique Provensi; Botelho, Eduardo Buganemi; Gomes, Thales Junior de Souza; Kist, Roger; Caceres, Rafael Andrade; Zanchi, Fernando Berton

doi:10.1186/s12859-023-05234-y

Cited by 14 publications

(4 citation statements)

References 24 publications

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“…MD simulation was conducted via the recently developed web portal Visual Dynamics ( http://visualdynamics.fiocruz.br/ ) via its Apo portal. 43 The operating parameters were set as follows: water model (SPC), box type (cubic), box distance 0.35 mm. The forcefield employed was AMBER 03 for 100 ns.…”

Section: Methodsmentioning

confidence: 99%

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Design of multi‐epitope chimeric vaccine against Monkeypox virus and SARS‐CoV‐2: A vaccinomics perspective

Al‐Madhagi,

Kanawati,

Tahan

2024

J Cellular Molecular Medi

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The current era we experience is full with pandemic infectious agents that no longer threatens the major local source but the whole globe. Almost the most emerging infectious agents are severe acute respiratory syndrome coronavirus‐2 (SARS CoV‐2), followed by monkeypox virus (MPXV). Since no approved antiviral drugs nor licensed active vaccines are yet available, we aimed to utilize immunoinformatics approach to design chimeric vaccine against the two mentioned viruses. This is the first study to deal with design divalent vaccine against SARS‐CoV‐2 and MPXV. ORF8, E and M proteins from Omicron SARS‐CoV‐2 and gp182 from MPXV were used as the protein precursor from which multi‐epitopes (inducing B‐cell, helper T cells, cytotoxic T cells and interferon‐ɣ) chimeric vaccine was contrived. The structure of the vaccine construct was predicted, validated, and docked to toll‐like receptor‐2 (TLR‐2). Moreover, its sequence was also used to examine the immune simulation profile and was then inserted into the pET‐28a plasmid for in silico cloning. The vaccine construct was probable antigen (0.543) and safe (non‐allergen) with strong binding energy to TLR‐2 (−1169.8 kcal/mol) and found to have significant immune simulation profile. In conclusion, the designed chimeric vaccine was potent and safe against SARS‐CoV‐2 and MPXV, which deserves further consideration.

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Section: Methodsmentioning

confidence: 99%

“…br/ ) via its Apo portal. 43 The operating parameters were set as follows: water model (SPC), box type (cubic), box distance 0.35 mm. The forcefield employed was AMBER 03 for 100 ns.…”

Section: Molecular Dynamics (Md) Simulationmentioning

confidence: 99%

Design of multi‐epitope chimeric vaccine against Monkeypox virus and SARS‐CoV‐2: A vaccinomics perspective

Al‐Madhagi,

Kanawati,

Tahan

2024

J Cellular Molecular Medi

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“…The I154F and W155R mutations were individually induced via in silico mutagenesis in the validated native FXN model using the Mutator Plugin 1.3 [ 82 ] within the Visual Molecular Dynamics (VMD) 1.9.3 software [ 83 ]. Molecular dynamics (MD) simulations of the native protein and variants were carried out using the GROMACS 2018.3 package [ 84 ], following methodologies established by our group [ 11 , 12 ]. The simulations were carried out in triplicate using the AMBER99SB-ILDN force field, known for accurately describing several structural and dynamic properties of proteins [ 85 ].…”

Section: Methodsmentioning

confidence: 99%

An In Silico Analysis of Genetic Variants and Structural Modeling of the Human Frataxin Protein in Friedreich’s Ataxia

Da Conceição,

Cabral,

Pereira

et al. 2024

IJMS

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Friedreich’s Ataxia (FRDA) stands out as the most prevalent form of hereditary ataxias, marked by progressive movement ataxia, loss of vibratory sensitivity, and skeletal deformities, severely affecting daily functioning. To date, the only medication available for treating FRDA is Omaveloxolone (Skyclarys®), recently approved by the FDA. Missense mutations within the human frataxin (FXN) gene, responsible for intracellular iron homeostasis regulation, are linked to FRDA development. These mutations induce FXN dysfunction, fostering mitochondrial iron accumulation and heightened oxidative stress, ultimately triggering neuronal cell death pathways. This study amalgamated 226 FXN genetic variants from the literature and database searches, with only 18 previously characterized. Predictive analyses revealed a notable prevalence of detrimental and destabilizing predictions for FXN mutations, predominantly impacting conserved residues crucial for protein function. Additionally, an accurate, comprehensive three-dimensional model of human FXN was constructed, serving as the basis for generating genetic variants I154F and W155R. These variants, selected for their severe clinical implications, underwent molecular dynamics (MD) simulations, unveiling flexibility and essential dynamic alterations in their N-terminal segments, encompassing FXN42, FXN56, and FXN78 domains pivotal for protein maturation. Thus, our findings indicate potential interaction profile disturbances in the FXN42, FXN56, and FXN78 domains induced by I154F and W155R mutations, aligning with the existing literature.

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“…In the recent years, molecular dynamics simulation has been considered as a major advancement in the field of drug discovery. [30] These simulations effectively analyze the behavior of proteins in full atomic detail considering the spaciotemporal scale. MD simulation of unbound IL-6Rα was conducted on GROMACS v2019.2.…”

Section: Molecular Dynamics Simulation Of Unbound Il-6rαmentioning

confidence: 99%

Molecular Design of Novel Inhibitor by Targeting IL‐6Rα using Combined Pharmacophore and Experimentally Verified Plant Products with Scaffold‐Hopping Techniques: A Dual Therapeutic Strategy for COVID‐19 and Cancer

Paul,

Roy,

Ray

2023

Chemistry & Biodiversity

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The IL‐6/IL‐6R/gp130 complex serves as a significant indicator of cytokine release syndrome in COVID‐19 and chronic inflammation, increasing the risk of cancer. Therefore, we identified IL‐6Rα as a potential target to block gp130 interaction. Notably, there has been no reception of approval for an orally available drug to serve this purpose, to date. In this study, we targeted IL‐6Rα to inhibit IL‐6Rα/gp130 interaction. The selection of the lead candidate L821 involved the amalgamation of three drug discovery approaches. This library was screened employing tertiary structure‐based pharmacophore models followed by molecular docking models, scaffold‐hopping, MM/PBSA as well as MM/GBSA analysis, and assessments of pKi and ADMET properties. After evaluating the binding interactions with key amino acids, 15 potential ligands were chosen, with the top ligand undergoing further investigation by means of molecular dynamics simulations. Considering the stability of the complexes, the strong interactions observed between ligand and residues of IL‐6Rα/gp130, and the favorable binding free energy calculations, L821 emerged as the prime candidate for inhibiting IL‐6Rα. Notably, L821 exhibited a docking‐based binding affinity of ‐9.5 kcal/mol. Our study presents L821 as a promising inhibitor for future in vitro analysis, potentially combatting SARS‐CoV‐2‐related cytokine storms and serving as an oncogenic drug therapy.

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Visual dynamics: a WEB application for molecular dynamics simulation using GROMACS

Cited by 14 publications

References 24 publications

Design of multi‐epitope chimeric vaccine against Monkeypox virus and SARS‐CoV‐2: A vaccinomics perspective

Design of multi‐epitope chimeric vaccine against Monkeypox virus and SARS‐CoV‐2: A vaccinomics perspective

An In Silico Analysis of Genetic Variants and Structural Modeling of the Human Frataxin Protein in Friedreich’s Ataxia

Molecular Design of Novel Inhibitor by Targeting IL‐6Rα using Combined Pharmacophore and Experimentally Verified Plant Products with Scaffold‐Hopping Techniques: A Dual Therapeutic Strategy for COVID‐19 and Cancer

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