scholarly journals Identification of novel TMPRSS2 inhibitors for COVID-19 using e-pharmacophore modelling, molecular docking, molecular dynamics and quantum mechanics studies

2021 ◽  
pp. 100758
Author(s):  
Abdulrahim A. Alzain ◽  
Fatima E. Albadwi
Keyword(s):  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Molecular Docking ◽  
Pharmacophore Modelling

scholarly journals Virtual screening of curcumin analogues as DYRK2 inhibitor: Pharmacophore analysis, molecular docking and dynamics, and ADME prediction

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 394
Author(s):  
La Ode Aman ◽  
Rahmana Emran Kartasasmita ◽  
Daryono Hadi Tjahjono
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Pharmacophore Model ◽  
Binding Pocket ◽  
26S Proteasome ◽  
Dynamics Simulation ◽  
Pharmacophore Modelling ◽  
Curcumin Analogues ◽  
Adme Prediction ◽  
Pharmacokinetic Properties

Background: Curcumin reduces the proliferation of cancer cells through inhibition of the DYRK2 enzyme, which is a positive regulator of the 26S proteasome. Methods: In the present work, curcumin analogues have been screened from the MolPort database using a pharmacophore model that comprised a ligand-based approach. The result of the screening was then evaluated by molecular docking and molecular dynamics based on binding the free energy of the interaction between each compound with the binding pocket of DYRK2. The hit compounds were then confirmed by absorption, distribution, metabolism, and excretion (ADME) prediction. Results: Screening of 7.4 million molecules from the MolPort database afforded six selected hit compounds. By considering the ADME prediction, three prospective curcumin analogues have been selected. These are:  2‐[2‐(1‐methylpyrazol‐4‐yl)ethyl]‐1H,5H,6H,7H,8H‐imidazo[4,5‐c]azepin‐4‐one (Molport-035-369-361), methyl 4‐(3‐hydroxy‐1,2‐oxazol‐5‐yl)piperidine‐1‐carboxylate (Molport-000-004-273) and (1S)‐1‐[5‐(furan‐3‐carbonyl)‐4H,6H,7H‐pyrazolo[1,5‐a]pyrazin‐2‐yl]ethanol (MolPort-035-585-822). Conclusion: Pharmacophore modelling, combined with molecular docking and molecular dynamics simulation, as well as ADME prediction were successfully applied to screen curcumin analogues from the MolPort database as DYRK2 inhibitors. All selected compounds that have better predicted pharmacokinetic properties than that of curcumin are considered for further study.

scholarly journals Virtual screening of the potential hCA XII inhibitors based on the pharmacophore modelling, molecular docking, MMGBSA and molecular dynamics simulations studies

2021 ◽  
Author(s):  
Mohammad M. Al-Sanea ◽  
Garri Chilingaryan ◽  
Narek Abelyan ◽  
Grigor Arakelov ◽  
Harutyun Sahakyan ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Pharmacophore Modelling ◽  
Therapeutic Value ◽  
Different Types ◽  
Pharmacological Target ◽  
Dynamics Simulations ◽  
Derivatives Of ◽  
Pharmacophore Models

Abstract Human carbonic anhydrase XII (hCA XII) has gained therapeutic value in the field of medicinal chemistry as a pharmacological target and biomarker for different types of cancer. Despite the fact that interaction features of hCAs inhibitors with the catalytic site of the enzyme are well described, lack in the selectivity of the traditional hCA inhibitors is an urgent issue. This study was devoted to the identification of novel potential hCA XII inhibitors using comprehensive set of computational approaches, including generation of structure-and ligand-based pharmacophore models, molecular docking, MMGBSA calculations and molecular dynamics simulations. As the results of the study multiple potential hCA inhibitors were identified. Along with the identified derivatives of the classical hCA inhibitors (have sulfonamide motifs), several compounds with alternative chemical scaffolds, that can be considered and further investigated as potential non-classical hCA XII inhibitors, were identified.

A Conserved Asparagine in a Ubiquitin Conjugating Enzyme Positions the Substrate for Nucleophilic Attack

2018 ◽  
Author(s):  
Walker M. Jones ◽  
Aaron G. Davis ◽  
R. Hunter Wilson ◽  
Katherine L. Elliott ◽  
Isaiah Sumner
Keyword(s):  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Molecular Mechanics ◽  
Reaction Rates ◽  
Nucleophilic Attack ◽  
Classical Molecular Dynamics ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

We present classical molecular dynamics (MD), Born-Oppenheimer molecular dynamics (BOMD), and hybrid quantum mechanics/molecular mechanics (QM/MM) data. MD was performed using the GPU accelerated pmemd module of the AMBER14MD package. BOMD was performed using CP2K version 2.6. The reaction rates in BOMD were accelerated using the Metadynamics method. QM/MM was performed using ONIOM in the Gaussian09 suite of programs. Relevant input files for BOMD and QM/MM are available.

Design of potential IKK-β inhibitors using molecular docking and molecular dynamics techniques for their anti-cancer potential

2020 ◽  
Vol 16 ◽  
Author(s):  
Salam Pradeep Singh ◽  
Iftikar Hussain ◽  
Bolin Kumar Konwar ◽  
Ramesh Chandra Deka ◽  
Chingakham Brajakishor Singh
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Md Simulation ◽  
Inflammatory Diseases ◽  
Binding Free Energy ◽  
Anti Cancer ◽  
Dietary Phytochemicals ◽  
Toxicity Analysis ◽  
The Stability ◽  
Stable Trajectory

Aim and Objective: To evaluate a set of seventy phytochemicals for their potential ability to bind the inhibitor of nuclear factor kappaB kinase beta (IKK-β) which is a prime target for cancer and inflammatory diseases. Materials and Methods: Seventy phytochemicals were screened against IKK-β enzyme using DFT-based molecular docking technique and the top docking hits were carried forward for molecular dynamics (MD) simulation protocols. The adme-toxicity analysis was also carried out for the top docking hits. Results: Sesamin, matairesinol and resveratrol were found to be the top docking hits with a total score of -413 kJ/mol, -398.11 kJ/mol and 266.73 kJ/mol respectively. Glu100 and Gly102 were found to be the most common interacting residues. The result from MD simulation observed a stable trajectory with a binding free energy of -107.62 kJ/mol for matairesinol, -120.37 kJ/mol for sesamin and -40.56 kJ/mol for resveratrol. The DFT calculation revealed the stability of the compounds. The ADME-Toxicity prediction observed that these compounds fall within the permissible area of Boiled-Egg and it does not violate any rule for pharmacological criteria, drug-likeness etc. Conclusion: The study interprets that dietary phytochemicals are potent inhibitors of IKK-β enzyme with favourable binding affinity and less toxic effects. In fact, there is a gradual rise in the use of plant-derived molecules because of its lesser side effects compared to chemotherapy. The study has also provided an insight by which the phytochemicals inhibited the IKK-β enzyme. The investigation would also provide in understanding the inhibitory mode of certain dietary phytochemicals in treating cancer.

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