Combined virtual screening, MMPBSA, molecular docking and dynamics studies against deadly anthrax: An in silico effort to inhibit Bacillus anthracis nucleoside hydrolase

Karami, Mohammad Reza; Jalali, Chiya; Mirzaie, Sako

doi:10.1016/j.jtbi.2017.03.010

Cited by 25 publications

(13 citation statements)

References 64 publications

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“…On the other hand, the molecular mechanical force field (MMFF)-based scoring functions, are physical and more accurate, but much less efficient. With the ever increasing computer power, MMFF-based free energy calculation methods, such as the endpoint MM-PB/GBSA (molecular mechanics-Poisson Boltzmann/ Generalized Born Surface Area) methods 2,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21] and the alchemical thermodynamic integration (TI) and free energy perturbation (FEP) methods, 22,23 have been extensively applied in structure-based drug discovery projects. Recently we've developed a hierarchical virtual screening (HVS)to balance the efficiency and accuracy and improve the success rate of rational drug design.…”

Section: Introductionmentioning

confidence: 99%

Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study

Wang

2020

Preprint

129

169

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The recent outbreak of novel coronavirus disease -19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D-structures of key virous proteins are resolved. Taking the advantage of a recently released crystal structure of COVID-19 protease in complex with a covalently-bonded inhibitor, N3, 1 I conducted virtual docking screening of approved drugs and drug candidates in clinical trials.For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an endpoint method called MM-PBSA-WSAS. 2-4 Several promising known drugs stand out as potential inhibitors of COVID-19 protease, including Carfilzomib, Eravacycline, Valrubicin, Lopinavir and Elbasvir. Carfilzomib, an approved anti-cancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, -13.82 kcal/mol. Streptomycin, an antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (-3.82 kcal/mol) is not nearly as low as that of the neutral form (-7.92 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of -12.86 kcal/mol. Detailed receptor-ligand interactions were analyzed and hot spots for the receptor-ligand binding were identified. I found that one hotspot residue HIS41, is a conserved residue across many viruses including COVID-19, SARS, MERS, and HCV. The findings of this study can facilitate rational drug design targeting the COVID-19 protease.

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Section: Introductionmentioning

confidence: 99%

Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study

Wang

2020

Preprint

129

169

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“…Docking is a tool for predicting the preferred direction of one molecule to another when bound to each other and constitute an energetically stable complex [47]. The 3D structure of vitamin D was sketched with HyperChem Version 8.0 (HyperCube Inc) followed by MM+ (molecular mechanics) and PM3 (semi-empirical) minimization and optimization.…”

Section: Molecular Docking Of Vitamin D Into the Vdrmentioning

confidence: 99%

“…For molecular docking runs, the default parameters were allocated. In each docking run, the pose with the lowest binding energy was chosen for MD study [47].…”

Section: Molecular Docking Of Vitamin D Into the Vdrmentioning

confidence: 99%

“…In the last system, totally six molecules of metformin were assigned in the MD box. The MD runs were performed with GROMACS 5.1 package and AMBER 99SB force field [47,49]. PROPKA 2.0 server [50] was occupied to calculate the pKa of VDR residues and assigning the proper ionization states of VDR ionizing groups.…”

Section: Simulation On Vdrmentioning

confidence: 99%

“…To restrict the bond lengths with a 2 fs time step, Linear Constraint Solver (LINCS) was occupied [58]. Each system was equilibrated under a constant volume (NVT) ensemble (100 ps) and a constant pressure (NPT) ensemble (100 ps) [47]. The equilibrated system from each run was subjected to 50 ns MD simulation.…”

Section: Simulation On Vdrmentioning

confidence: 99%

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Vitamin D as a modulating agent of metformin and insulin in patients with type 2 diabetes

Abdi¹,

Movahedi²,

Nikje³

et al. 2019

jrp

Self Cite

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Diabetes, which is one of the most important health challenges for humankind, is associated with impaired glucose metabolism. Diabetes mellitus (DM) includes two major types of diabetes, type 1 (T1DM) and type 2 (T2DM). In this study, in the beginning, interventional and experimental studies were performed on 45 patients with T2DM, and the modulating effects of vitamin D were evaluated on the biochemical parameters of patients with the restricted diet, consuming metformin or insulin. With regard to our experimental results, the combination treatment of metformin/ vitamin D or insulin/ vitamin D can reduce the fasting blood sugar (FBS). A combination of vitamin D with insulin decreases the insulin resistance and raises the insulin sensitivity in patients with T2DM. The combination treatment of vitamin D and metformin led to a decrease in the level of mRNA of GLUT4, and also it's trafficking from the cytosol to the plasma membrane. At the second phase of the present study, molecular dynamics (MD), molecular docking, MM/PBSA, and QM/MM were occupied to examine the structural behavior of VDR, in the free or ligand bound state, during 50 ns. The MD results exhibited that in the presence of metformin, the flexibility of residues comprising helix 12 from vitamin D-bound VDR was decreased. In addition, metformin decreased the radius of gyration of agonist-bound VDR. In addition, QM/MM results showed that metformin diminished the binding free energy between VDR and vitamin D. Our computational data demonstrated that metformin, in the presence of vitamin D, reinforces the interaction between VDR and its co-activator protein.

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Porphyrin‐based ligand interaction with G‐quadruplex: Metal cation effects

Otovat

Bozorgmehr

Mahmoudi

et al. 2023

J of Molecular Recognition

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The G‐quadruplex planar‐ligand complex is used to detect heavy metal cations such as Ag+, Cu2+, Pb2+, Hg2+, organic molecules, nucleic acids, and proteins. The interaction of the three planar porphyrins (L1), 5,10,15,20‐tetrakis (1‐ethyl‐1‐λ4‐pyridine‐4‐yl) porphyrin (L2), and 5,10,15,20‐tetrakis (1‐methyl‐1‐λ4‐pyridine‐4‐yl) porphyrin (L3), coming from the porphyrin family, with G‐quadruplex obtained from human DNA telomeres in the presence of lithium, sodium, potassium, rubidium, cesium, magnesium, and calcium ions was studied by molecular dynamics simulation. When G‐quadruplex containing divalent ions of magnesium and calcium interacts with L1, L2, and L3 ligands, the hydrogen bonds of the lower G‐quadruplex sheet are more affected by ligands and the distance between guanines in the lower tetrad increases. In the case of G‐quadruplex interactions containing monovalent ions with ligands, the hydrogen bond between the sheets does not follow a specific trend. For example, in the presence of lithium ions, the upper and middle sheets are more affected by ligands, while they are less affected by ligands in the presence of sodium. The binding pocket and the binding energy of the three ligands to the G‐quadruplex were also obtained in the various systems. The results show that ligands make the G‐quadruplex more stable through the penetration between the sheets and the interaction with the loops. Among the ligands mentioned, the interaction level of the ligand L2 is greater than the others. Our calculations are consistent with the previous experimental observations so that it can help to understand the molecular mechanism of porphyrin interaction and its derivatives with the G‐quadruplex.

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Combined virtual screening, MMPBSA, molecular docking and dynamics studies against deadly anthrax: An in silico effort to inhibit Bacillus anthracis nucleoside hydrolase

Cited by 25 publications

References 64 publications

Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study

Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study

Vitamin D as a modulating agent of metformin and insulin in patients with type 2 diabetes

Porphyrin‐based ligand interaction with G‐quadruplex: Metal cation effects

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