Gaussian-Accelerated Molecular Dynamics with the Weighted Ensemble Method: A Hybrid Method Improves Thermodynamic and Kinetic Sampling

Gaussian-accelerated molecular dynamics (GaMD) is a well-established enhanced sampling method for molecular dynamics simulations that effectively samples the potential energy landscape of the system by adding a boost potential, which smoothens the surface and lowers the energy barriers between states. GaMD is unable to give time-dependent properties such as kinetics directly. On the other hand, the weighted ensemble (WE) method can efficiently sample transitions between states with its many weighted trajectories, which directly yield rates and pathways. However, convergence to equilibrium conditions remains a challenge for the WE method. Hence, we have developed a hybrid method that combines the two methods, wherein GaMD is first used to sample the potential energy landscape of the system and WE is subsequently used to further sample the potential energy landscape and kinetic properties of interest. We show that the hybrid method can sample both thermodynamic and kinetic properties more accurately and quickly compared to using either method alone.

Automated summary

Gaussian-accelerated molecular dynamics (GaMD) and weighted ensemble (WE) methods have their own advantages but also limitations, therefore combining these two methods can sample both the potential energy landscape and kinetic properties of a system more accurately and quickly.