An accurate and efficient NPT ensemble molecular dynamics simulation method

Abstract

The accuracy of the NPT ensemble is important for obtaining accurate biomolecular dynamics and thermodynamic properties in molecular dynamics simulations. Although considerable effort has been devoted to improving its accuracy, most studies have not been rigorously validated. We introduce a novel NPT ensemble method that meticulously optimizes the critical components that significantly improve accuracy and efficiency, especially in pressure regulation. In particular, our method (i) incorporated the Martyna–Tobias–Klein correction terms into the equations of motion for the desired NPT partition function, (ii) utilized the Langevin dynamics algorithm for barostat equilibration to reduce mass-dependent ringing effects, (iii) integrated the barostat using the BAOAB scheme to ensure minimal error and high stability, and (iv) employed molecular pressure to optimize the constraint calculation. Tests showed that our NPT ensemble method achieved accurate and well-converged pressure and temperature control in both protein solutions and pure water systems.