High preorganization of large lipophilic surfaces common to two complexing partners provides high binding free energies that vary dramatically with changes in organic solvent composition

1990 ◽  
Vol 112 (3) ◽  
pp. 1255-1256 ◽  
Author(s):  
Judi A. Bryant ◽  
John L. Ericson ◽  
Donald J. Cram
Keyword(s):  
Organic Solvent ◽  
Solvent Composition ◽  
Free Energies ◽  
High Binding ◽  
Binding Free Energies

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.

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

scholarly journals Doxorubicin Encapsulation in Carbon Nanotubes Having Haeckelite or Stone–Wales Defects as Drug Carriers: A Molecular Dynamics Approach

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1586
Author(s):  
Leonor Contreras ◽  
Ignacio Villarroel ◽  
Camila Torres ◽  
Roberto Rozas
Keyword(s):  
Carbon Nanotubes ◽  
Molecular Dynamics ◽  
Drug Delivery Systems ◽  
Nitrogen Doping ◽  
Drug Carriers ◽  
Acidic Ph ◽  
Free Energies ◽  
Interaction Forces ◽  
Chiral Nanotubes ◽  
Binding Free Energies

Doxorubicin (DOX), a recognized anticancer drug, forms stable associations with carbon nanotubes (CNTs). CNTs when properly functionalized have the ability to anchor directly in cancerous tumors where the release of the drug occurs thanks to the tumor slightly acidic pH. Herein, we study the armchair and zigzag CNTs with Stone–Wales (SW) defects to rank their ability to encapsulate DOX by determining the DOX-CNT binding free energies using the MM/PBSA and MM/GBSA methods implemented in AMBER16. We investigate also the chiral CNTs with haeckelite defects. Each haeckelite defect consists of a pair of square and octagonal rings. The armchair and zigzag CNT with SW defects and chiral nanotubes with haeckelite defects predict DOX-CNT interactions that depend on the length of the nanotube, the number of present defects and nitrogen doping. Chiral nanotubes having two haeckelite defects reveal a clear dependence on the nitrogen content with DOX-CNT interaction forces decreasing in the order 0N > 4N > 8N. These results contribute to a further understanding of drug-nanotube interactions and to the design of new drug delivery systems based on CNTs.

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