Development of parameters compatible with the CHARMM36 force field for [Fe
 4
 S
 4
 ]
 2+
 clusters and molecular dynamics simulations of adenosine-5’-phosphosulfate reductase in GROMACS 2019

Silva, Talis Uelisson da; Pougy, Karina de Carvalho; Albuquerque, Magaly Girão; Lima, Camilo Henrique da Silva; Machado, Sérgio de Paula

doi:10.1080/07391102.2020.1847687

Cited by 34 publications

(16 citation statements)

References 71 publications

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“…The analysis of the simulated trajectories and structures was carried out with the built-in tools of the GROMACS program. The PME method was applied to calculate the electrostatic interactions and the conjugate gradient algorithm 127 , 128 was used to constrain covalent bonds involving hydrogen. Using the CPPTRAJ tool 129 , it was possible to extract the necessary information for the creation of Root Mean Square Deviation (RMSD) graphs 130 , 131 and free energy tables 132 , all as a function of time.…”

Section: Methodsmentioning

confidence: 99%

Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics

Alencar

Arouche

Neto

et al. 2022

Sci Rep

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The new coronavirus, SARS-CoV-2, caused the COVID-19 pandemic, characterized by its high rate of contamination, propagation capacity, and lethality rate. In this work, we approach the use of phthalocyanines as an inhibitor of SARS-CoV-2, as they present several interactive properties of the phthalocyanines (Pc) of Cobalt (CoPc), Copper (CuPc) and without a metal group (NoPc) can interact with SARS-CoV-2, showing potential be used as filtering by adsorption on paints on walls, masks, clothes, and air conditioning filters. Molecular modeling techniques through Molecular Docking and Molecular Dynamics were used, where the target was the external structures of the virus, but specifically the envelope protein, main protease, and Spike glycoprotein proteases. Using the g_MM-GBSA module and with it, the molecular docking studies show that the ligands have interaction characteristics capable of adsorbing the structures. Molecular dynamics provided information on the root-mean-square deviation of the atomic positions provided values between 1 and 2.5. The generalized Born implicit solvation model, Gibbs free energy, and solvent accessible surface area approach were used. Among the results obtained through molecular dynamics, it was noticed that interactions occur since Pc could bind to residues of the active site of macromolecules, demonstrating good interactions; in particular with CoPc. Molecular couplings and free energy showed that S-gly active site residues interacted strongly with phthalocyanines with values of − 182.443 kJ/mol (CoPc), 158.954 kJ/mol (CuPc), and − 129.963 kJ/mol (NoPc). The interactions of Pc's with SARS-CoV-2 may predict some promising candidates for antagonists to the virus, which if confirmed through experimental approaches, may contribute to resolving the global crisis of the COVID-19 pandemic.

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Section: Methodsmentioning

confidence: 99%

Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics

Alencar

Arouche

Neto

et al. 2022

Sci Rep

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“…Both the molecular docking studies using MOE 2014.09 suite (Vilar et al, 2008 ) and molecular dynamics simulation using the GROMACS-2019 software package and CHARMM36 force field (da Silva et al, 2020 ) were applied in this study.…”

Section: Methodsmentioning

confidence: 99%

“…The best-docking scored models of the most promising leads, alacepril and lisinopril, in complex with h ACE2 protein were chosen as starting coordinates for 100 ns all-atom molecular dynamics simulation using a GROMACS-2019 software package (GNU, General Public License; http://www.gromacs.org ) and CHARMM36 force field (da Silva et al, 2020 ). Each ligand–protein complex was solvated within a cubic box of the transferable intermolecular potential with a three-points (TIP3P) water model (100 × 100 × 100 Å) allowing a minimum of 10 Å marginal distance between protein and each side of the 3D box (Izadi et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

et al. 2021

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The rapid and global spread of a new human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. We review current information concerning the global health issue of COVID-19 including promising approved drugs, e.g., human angiotensin-converting enzyme inhibitors (hACEIs). Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2. Alacepril and lisinopril were found to interact with human angiotensin-converting enzyme 2 (hACE2), the host entranceway for SARS-CoV-2 spike protein, through exhibiting the most acceptable rmsd_refine values and the best binding affinity through forming a strong hydrogen bond with Asn90, which is assumed to be essential for the activity, as well as significant extra interactions with other receptor-binding residues. Furthermore, molecular dynamics (MD) simulations followed by calculation of the binding free energy were also carried out for the most promising two ligand-pocket complexes from docking studies (alacepril and lisinopril) to clarify some information on their thermodynamic and dynamic properties and confirm the docking results as well. These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds.

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“…The twelve isolated compounds were examined for their binding potentials towards SARS-CoV-2 main protease in comparison to its N3 inhibitor via molecular docking through MOE 2019 suite 31 and molecular dynamics simulation using a GROMACS-2019 software package and CHARMM36 force field 32 .…”

Section: Methodsmentioning

confidence: 99%

“…The top-dock models of the most promising leads (Calendulaglycoside A (SAP5) and Osteosaponin-I (SAP8)), as well as N3 in complex with SARS-CoV-2 main protease, were chosen as starting coordinates for 100 ns all-atoms molecular dynamic (MD) simulation using a GROMACS-2019 software package (GNU, General Public License; http://www.gromacs.org ) and CHARMM36 force field 32 . 28 , 29 Regarding the investigated ligands, the CHARMM force field parameters were automatically generated using the CHARMM General Force Field (CGenFF) program (ParamChem project; https://cgenff.umaryland.edu/ ).…”

Section: Methodsmentioning

confidence: 99%

Calendulaglycoside A showing potential activity against SARS-CoV-2 main protease: Molecular docking, molecular dynamics, and SAR studies

Zaki

Ashour

Elhady

et al. 2022

Journal of Traditional and Complementary Medicine

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Background and Aim The discovery of drugs capable of inhibiting SARS-CoV-2 is a priority for human beings due to the severity of the global health pandemic caused by COVID-19. To this end, natural products can provide therapeutic alternatives that could be employed as an effective safe treatment for COVID-19. Experimental procedure Twelve compounds were isolated from the aerial parts of C. officinalis L. and investigated for their inhibitory activities against SARS-CoV-2 M pro compared to its co-crystallized N3 inhibitor using molecular docking studies. Furthermore, a 100 ns MD simulation was performed for the most active two promising compounds, Calendulaglycoside A (SAP5) and Osteosaponin-I (SAP8). Results and Conclusion At first, molecular docking studies showed interesting binding scores as compared to the N3 inhibitor. Calendulaglycoside A (SAP5) achieved a superior binding than the co-crystallized inhibitor indicating promising affinity and intrinsic activity towards the M pro of SARS-CoV-2 as well. Moreover, findings illustrated preferential stability for SAP5 within the M pro pocket over that of N3 beyond the 40 ns MD simulation course. Structural preferentiality for triterpene-M pro binding highlights the significant role of 17 β -glucosyl and carboxylic 3 α -galactosyl I moieties through high electrostatic interactions across the MD simulation trajectories. Furthermore, this study clarified a promising SAR responsible for the antiviral activity against the SARS-CoV-2 M pro and the design of new drug candidates targeting it as well. The above findings could be promising for fast examining the previously isolated triterpenes both pre-clinically and clinically for the treatment of COVID-19.

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Development of parameters compatible with the CHARMM36 force field for [Fe ₄ S ₄ ] ²⁺ clusters and molecular dynamics simulations of adenosine-5’-phosphosulfate reductase in GROMACS 2019

Cited by 34 publications

References 71 publications

Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics

Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

Calendulaglycoside A showing potential activity against SARS-CoV-2 main protease: Molecular docking, molecular dynamics, and SAR studies

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Development of parameters compatible with the CHARMM36 force field for [Fe 4 S 4 ] 2+ clusters and molecular dynamics simulations of adenosine-5’-phosphosulfate reductase in GROMACS 2019

Cited by 34 publications

References 71 publications

Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics

Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

Calendulaglycoside A showing potential activity against SARS-CoV-2 main protease: Molecular docking, molecular dynamics, and SAR studies

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Development of parameters compatible with the CHARMM36 force field for [Fe ₄ S ₄ ] ²⁺ clusters and molecular dynamics simulations of adenosine-5’-phosphosulfate reductase in GROMACS 2019