A Benchmark of Electrostatic Methods Performance in Relative Binding Free Energy Calculations

16 February 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


Relative free energy calculations are fast becoming a critical part of early stage pharmaceu- tical design, making it important to know how to obtain the best performance with these calculations in applications which could span hundreds of calculations and molecules. In this work, we compared two different treatments of long-range electrostatics, Particle Mesh Ewald (PME) and Reaction Field (RF), in relative binding free energy calculations using a non-equilibrium switching protocol. We found simulations using RF achieve comparable re- sults as those using PME but gain more efficiency when using CPU and similar performance using GPU. The results from this work encourage more use of RF in molecular simulations.


Relative Binding Free Energy Calculations
nonequilibrium free energy calculations
long-range electrostatics
Particle Mesh Ewald method
Reaction Field method
Alchemical Free Energy Calculations


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