Generalised canonical–isokinetic ensemble: speeding up multiscale molecular dynamics and coupling with 3D molecular theory of solvation

We have proposed a new canonical–isokinetic ensemble for efficient sampling of conformational space in molecular dynamics (MD) simulations which leads to the optimised isokinetic Nose–Hoover (OIN) chain algorithm for atomic and molecular systems. We applied OIN to multiple time step (MTS) MD simulations of the rigid and flexible models of water to demonstrate its advantage over the standard canonical, isokinetic and canonical–isokinetic ensembles. With the stabilising effect of OIN thermostatting in MTS-MD, gigantic outer time steps up to picoseconds can be employed to accurately calculate equilibrium and conformational properties. Furthermore, we developed the atomic version of OIN for MTS-MD of a biomolecule in a solvent potential of mean force obtained at sequential MD steps by using the molecular theory of solvation, aka three-dimensional reference interaction site model with the Kovalenko–Hirata closure (3D-RISM-KH). The solvation forces are obtained analytically by converging the 3D-RISM-KH integral...