Simulated Solute Tempering 2

Molecular dynamics (MD) simulations are powerful tools for studying the movement and interactions of molecules, but they can be computationally expensive, especially for large biomolecules like proteins. This is problematic because accurately simulating the motions of these molecules is key to understanding their function. Enhanced sampling methods, such as Simulated Tempering (ST), temperature Replica Exchange Molecular Dynamics (REMD) and Replica Exchange with Solute Tempering (REST and REST2), have been developed to overcome this challenge by improving the efficiency of MD simulations. This article presents a new improved sampling method called Simulated Solvent Tempering 2 (SST2), which builds on the strengths of ST and REST2. SST2 selectively scales the interactions within a biomolecule and with its surrounding environment, effectively accelerating the exploration of its different structural states and their stability at different temperatures. SST2 was tested on three different systems (Chignolin CLN025, Trp-Cage, and a protein-peptide complex, p97/PNGase) and was found to achieve comparable or superior sampling efficiency to ST while requiring fewer temperature rungs. In particular, SST2 is well suited to the study of large biomolecular systems, making it a valuable tool for investigating a wide range of biomolecular processes, from protein folding to drug binding.