Isokinetic approach in logarithmic mean-force dynamics for on-the-fly free energy reconstruction

Highlights: • LogMFD is extended to incorporate the isokinetic dynamics. • The isokinetic LogMFD approach requires no parameter for thermostatting. • The isokinetic approach makes it easier to set up and undertake LogMFD calculations. • The validity of the isokinetic algorithm in LogMFD is confirmed by a benchmark system. Logarithmic mean-force dynamics (LogMFD) is one of free energy calculation methods that utilize fictitious dynamical variables for efficient conformational sampling. In this study, we extend the LogMFD method to incorporate the isokinetic dynamics for the fictitious dynamical variables. The isokinetic LogMFD approach requires no additional parameter for thermostatting and it obviates the issue associated with the dynamics of the thermostat variable in Nosé-Hoover type thermostats. These virtues therefore make it easier to set up and undertake LogMFD calculations. The validity of the isokinetic algorithm introduced in LogMFD is examined by a benchmark system of alanine dipeptide in explicit water.