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

Relative free energy calculations are fast becoming a critical part of early stage pharmaceutical design, making it important to know how to obtain the best performance with these calculations in applications that 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 nonequilibrium switching protocol. We found simulations using RF achieve comparable results to 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.

Automated summary

Relative free energy calculations are becoming critical in early pharmaceutical design, and this study compared two methods for long-range electrostatics, finding that RF simulations are more efficient and encouraging their increased use in molecular simulations.