scholarly journals Icotinib, Almonertinib, and Olmutinib: A 2D Similarity/Docking-based Study to Predict the Potential Binding Modes and Interactions into EGFR

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6423
Author(s):  
Faisal Almalki ◽  
Ahmed Shawky ◽  
Ashraf Abdalla ◽  
Ahmed Gouda
Keyword(s):  
Similarity Search ◽  
Docking Study ◽  
Binding Modes ◽  
Free Energies ◽  
Binding Characteristics ◽  
High Binding ◽  
Egfr Ligands ◽  
Potential Binding ◽  
Michael Acceptor ◽  
Binding Free Energies

In the current study, a 2D similarity/docking-based study was used to predict the potential binding modes of icotinib, almonertinib, and olmutinib into EGFR. The similarity search of icotinib, almonertinib, and olmutinib against a database of 154 EGFR ligands revealed the highest similarity scores with erlotinib (0.9333), osimertinib (0.9487), and WZ4003 (0.8421), respectively. In addition, the results of the docking study of the three drugs into EGFR revealed high binding free energies (Gb = −6.32 to −8.42 kcal/mol) compared to the co-crystallized ligands (Gb = −7.03 to −8.07 kcal/mol). Analysis of the top-scoring poses of the three drugs was done to identify their potential binding modes. The distances between Cys797 in EGFR and the Michael acceptor sites in almonertinib and olmutinib were determined. In conclusion, the results could provide insights into the potential binding characteristics of the three drugs into EGFR which could help in the design of new more potent analogs.

Theoretical study of the binding profile of an allosteric modulator NS-1738 with a chimera structure of the α7 nicotinic acetylcholine receptor

2016 ◽  
Vol 18 (40) ◽  
pp. 28003-28009 ◽  
Author(s):  
Guanglin Kuang ◽  
Xu Wang ◽  
Christer Halldin ◽  
Agneta Nordberg ◽  
Bengt Långström ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Theoretical Study ◽  
Allosteric Modulator ◽  
Simulation Methods ◽  
Binding Modes ◽  
Free Energies ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Binding Free Energies

The binding modes and binding free energies of the allosteric modulator NS-1738 with a chimera structure of the α7 nicotinic acetylcholine receptor have been studied by molecular simulation methods.

scholarly journals Some novel insights into the binding of oseltamivir and zanamivir to H5N1 and N9 influenza virus neuraminidases: A homology modeling and flexible docking study

2009 ◽  
Vol 74 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Marija Mihajlovic ◽  
Petar Mitrasinovic
Keyword(s):  
Homology Modeling ◽  
Protein Structures ◽  
Three Dimensional ◽  
Docking Study ◽  
Energy Difference ◽  
Am1 Method ◽  
Free Energies ◽  
Flexible Docking ◽  
Three Dimensional Models ◽  
Binding Free Energies

In the context of the recent pandemic threat by the worldwide spread of H5N1 avian influenza, novel insights into the mechanism of ligand binding and interaction between various inhibitors (zanamivir - ZMV, oseltamivir - OTV, 2,3-didehydro-2-deoxy-N-acetylneuraminic acid - DANA, peramivir - PMV) and neuraminidases (NA) are of vital importance for the structure-based design of new anti-viral drugs. To address this issue, three-dimensional models of H5N1-NA and N9-NA were generated by homology modeling. Traditional residues within the active site throughout the family of NA protein structures were found to be highly conserved in H5N1-NA. A subtle variation between lipophilic and hydrophilic environments in H5N1-NA with respect to N9-NA was observed, thus shedding more light on the high resistance of some H5N1 strains to various NA inhibitors. Based on these models, an ArgusLab4/AScore flexible docking study was performed. The conformational differences between OTV bound to H5N1-NA and OTV bound to N9-NA were structurally identified and quantified. A slight difference of less than 1 kcal mol-1 between the OTV-N9 and OTV-N1 binding free energies is in agreement with the experimentally predicted free energy difference. The conformational differences between ZMV and OTV bound to either H5N1-NA or N9-NA were structurally identified. The binding free energies of the ZMV complexes, being slightly higher than those of OTV, are not in agreement with what was previously proposed using homology modeling. The differences between ZMV and OTV are suggested to be ascribed to the presence/absence of Asn166 in the active cavity of ZMV/OTV in H5N1-NA, and to the presence/absence of Ser165 in the binding site of ZMV/OTV in N9-NA. The charge distribution was evaluated using the semi-empirical AM1 method. The trends of the AM1 charges of the ZMV and OTV side chains in the complexes deviate from those previously reported.

scholarly journals In Silico Screening of Semi-Synthesized Compounds as Potential Inhibitors for SARS-CoV-2 Papain-Like Protease: Pharmacophoric Features, Molecular Docking, ADMET, Toxicity and DFT Studies

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6593
Author(s):  
Mohamed S. Alesawy ◽  
Eslam B. Elkaeed ◽  
Aisha A. Alsfouk ◽  
Ahmed M. Metwaly ◽  
Ibrahim. H. Eissa
Keyword(s):  
Structural Features ◽  
Docking Studies ◽  
Proteolytic Processing ◽  
Binding Modes ◽  
Free Energies ◽  
Essential Enzyme ◽  
Potential Inhibitors ◽  
Molecular Electrostatic Potential Maps ◽  
Better Than ◽  
Binding Free Energies

Papain-like protease is an essential enzyme in the proteolytic processing required for the replication of SARS-CoV-2. Accordingly, such an enzyme is an important target for the development of anti-SARS-CoV-2 agents which may reduce the mortality associated with outbreaks of SARS-CoV-2. A set of 69 semi-synthesized molecules that exhibited the structural features of SARS-CoV-2 papain-like protease inhibitors (PLPI) were docked against the coronavirus papain-like protease (PLpro) enzyme (PDB ID: (4OW0). Docking studies showed that derivatives 34 and 58 were better than the co-crystallized ligand while derivatives 17, 28, 31, 40, 41, 43, 47, 54, and 65 exhibited good binding modes and binding free energies. The pharmacokinetic profiling study was conducted according to the four principles of the Lipinski rules and excluded derivative 31. Furthermore, ADMET and toxicity studies showed that derivatives 28, 34, and 47 have the potential to be drugs and have been demonstrated as safe when assessed via seven toxicity models. Finally, comparing the molecular orbital energies and the molecular electrostatic potential maps of 28, 34, and 47 against the co-crystallized ligand in a DFT study indicated that 28 is the most promising candidate to interact with the target receptor (PLpro).

Molecular Docking Studies on Isocytosine Analogues as Xanthine Oxidase Inhibitors

Drug Research ◽  
2018 ◽  
Vol 68 (07) ◽  
pp. 395-402 ◽  
Author(s):  
Subhajit Roy ◽  
Bawneet Narang ◽  
Manish Gupta ◽  
Vikrant Abbot ◽  
Virender Singh ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Docking Studies ◽  
Binding Modes ◽  
Free Energies ◽  
Flexible Docking ◽  
Docking Simulations ◽  
Xanthine Oxidase Inhibitors ◽  
Best Fit ◽  
Insight Into ◽  
Binding Free Energies

AbstractFlexible docking simulations were carried out on a series of isocytosine analogs as xanthine oxidase (XO) inhibitors. This was done by analysing the interaction of these compounds at the active site of XO. The binding free energies of the analogs were calculated using GoldScore. The binding modes of the best-fit conformation were studied, providing some handy important interactions. The results obtained henceforth provided an insight into the pharmacophoric structural requirements for XO inhibition for this class of molecules.

scholarly journals Molecular Docking Study of Some Nitro Diazo Dye Derivatives as Antiviral Candidates of COVID-19

2021 ◽  
pp. 8-15
Author(s):  
Mohammed Hadi Al–Douh ◽  
Elham Abdalrahem Bin Selim ◽  
Hassan Hadi Abdallah ◽  
Hewa Y. Abdullah ◽  
Aisha Khalid Al–Bakri ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Viral Proteins ◽  
Docking Study ◽  
Free Energies ◽  
Molecular Docking Study ◽  
Docking Method ◽  
Diazo Dye ◽  
Diazo Dyes ◽  
Binding Free Energies ◽  
Molecular Docking Method

In this study, the computerized molecular docking method was used to investigate the interactions of five nitro diazo dye derivatives 1-5 with COVID-19, CLpro, RAF and PLpro as very important viral proteins to target the coronavirus SARS-CoV-2. Among the used diazo dyes, compound 5 showed the highest binding free energies and the lowest inhibition constants Ki with all studied proteins, and it exhibits a large effect to inhibit the activities of the RAF and COVID-19. Therefore, compound 5 may be useful as an antiviral candidate that worth more trials for COVID-19 disease. The binding sites of compound 5 with the tested viral proteins were evaluated.

scholarly journals Automation of absolute protein-ligand binding free energy calculations for docking refinement and compound evaluation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Germano Heinzelmann ◽  
Michael K. Gilson
Keyword(s):  
Free Energy ◽  
Early Stage ◽  
Binding Free Energy ◽  
Low Cost ◽  
Free Energy Calculations ◽  
Free Energies ◽  
Energy Calculations ◽  
Drug Candidates ◽  
Binding Free Energy Calculations ◽  
Binding Free Energies

AbstractAbsolute binding free energy calculations with explicit solvent molecular simulations can provide estimates of protein-ligand affinities, and thus reduce the time and costs needed to find new drug candidates. However, these calculations can be complex to implement and perform. Here, we introduce the software BAT.py, a Python tool that invokes the AMBER simulation package to automate the calculation of binding free energies for a protein with a series of ligands. The software supports the attach-pull-release (APR) and double decoupling (DD) binding free energy methods, as well as the simultaneous decoupling-recoupling (SDR) method, a variant of double decoupling that avoids numerical artifacts associated with charged ligands. We report encouraging initial test applications of this software both to re-rank docked poses and to estimate overall binding free energies. We also show that it is practical to carry out these calculations cheaply by using graphical processing units in common machines that can be built for this purpose. The combination of automation and low cost positions this procedure to be applied in a relatively high-throughput mode and thus stands to enable new applications in early-stage drug discovery.

scholarly journals Protein-ligand free energies of binding from full-protein DFT calculations: convergence and choice of exchange-correlation functional

2021 ◽  
Author(s):  
Lennart Gundelach ◽  
Christofer S Tautermann ◽  
Thomas Fox ◽  
Chris-Kriton Skylaris
Keyword(s):  
Drug Discovery ◽  
Ligand Binding ◽  
Dft Calculations ◽  
Quantum Mechanical ◽  
Free Energies ◽  
Ligand Interaction ◽  
Exchange Correlation ◽  
Ligand Free ◽  
Protein Ligand Interaction ◽  
Binding Free Energies

The accurate prediction of protein-ligand binding free energies with tractable computational methods has the potential to revolutionize drug discovery. Modeling the protein-ligand interaction at a quantum mechanical level, instead of...

A computational analysis of the binding free energies of apoptosis signal-regulating kinase 1 inhibitors from different chemotypes

2021 ◽  
pp. 1-11
Author(s):  
Galyna P. Volynets ◽  
Larysa V. Pletnova ◽  
Vladislav M. Sapelkin ◽  
Oleksandr V. Savytskyi ◽  
Sergiy M. Yarmoluk
Keyword(s):  
Computational Analysis ◽  
Free Energies ◽  
Binding Free Energies
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