Impact of Different Automated Binding Pose Generation Approaches on Relative Binding Free Energy Simulations

2020 ◽  
Vol 60 (3) ◽  
pp. 1432-1444 ◽  
Author(s):  
Daniel Cappel ◽  
Steven Jerome ◽  
Gerhard Hessler ◽  
Hans Matter
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Relative Binding ◽  
Energy Simulations

scholarly journals TIES 20: Relative Binding Free Energy with a Flexible Superimposition Algorithm and Partial Ring Morphing

2021 ◽  
Vol 17 (2) ◽  
pp. 1250-1265
Author(s):  
Mateusz K. Bieniek ◽  
Agastya P. Bhati ◽  
Shunzhou Wan ◽  
Peter V. Coveney
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Relative Binding

scholarly journals New Tools for Conformational and Binding Free Energy Simulations

2019 ◽  
Vol 116 (3) ◽  
pp. 142a
Author(s):  
Giacomo Fiorin ◽  
Grace Brannigan ◽  
Jérôme Hénin
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Energy Simulations

scholarly journals Alchemical Free Energy Estimators and Molecular Dynamics Engines: Accuracy, Precision and Reproducibility

2021 ◽  
Author(s):  
Alexander Wade ◽  
Agastya Bhati ◽  
Shunzhou Wan ◽  
Peter Coveney
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Binding Free Energy ◽  
Thermodynamic Integration ◽  
Free Energy Perturbation ◽  
Free Energies ◽  
Ensemble Averaging ◽  
Relative Binding ◽  
Energy Perturbation ◽  
Binding Free Energies

The binding free energy between a ligand and its target protein is an essential quantity to know at all stages of the drug discovery pipeline. Assessing this value computationally can offer insight into where efforts should be focused in the pursuit of effective therapeutics to treat myriad diseases. In this work we examine the computation of alchemical relative binding free energies with an eye to assessing reproducibility across popular molecular dynamics packages and free energy estimators. The focus of this work is on 54 ligand transformations from a diverse set of protein targets: MCL1, PTP1B, TYK2, CDK2 and thrombin. These targets are studied with three popular molecular dynamics packages: OpenMM, NAMD2 and NAMD3. Trajectories collected with these packages are used to compare relative binding free energies calculated with thermodynamic integration and free energy perturbation methods. The resulting binding free energies show good agreement between molecular dynamics packages with an average mean unsigned error between packages of 0.5 $kcal/mol$ The correlation between packages is very good with the lowest Spearman's, Pearson's and Kendall's tau correlation coefficient between two packages being 0.91, 0.89 and 0.74 respectively. Agreement between thermodynamic integration and free energy perturbation is shown to be very good when using ensemble averaging.

scholarly journals FEPrepare: A Web-Based Tool for Automating the Setup of Relative Binding Free Energy Calculations

2021 ◽  
Author(s):  
Stamatia Zavitsanou ◽  
Alexandros Tsengenes ◽  
Michail Papadourakis ◽  
Giorgio Amendola ◽  
Alexios Chatzigoulas ◽  
...  
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Web Based ◽  
Energy Calculations ◽  
Relative Binding ◽  
Binding Free Energy Calculations
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