How Well Does the Extended Linear Interaction Energy Method Perform in Accurate Binding Free Energy Calculations?

2020 ◽  
Vol 60 (12) ◽  
pp. 6624-6633
Author(s):  
Dongxiao Hao ◽  
Xibing He ◽  
Beihong Ji ◽  
Shengli Zhang ◽  
Junmei Wang
Keyword(s):  
Free Energy ◽  
Interaction Energy ◽  
Energy Method ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Linear Interaction ◽  
Linear Interaction Energy ◽  
Energy Calculations ◽  
Binding Free Energy Calculations

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.

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