Calculation of temperature dependence of free energy caused by potential function changes

We propose a method to calculate the temperature dependence of free energy caused by potential function changes by combining λ dynamics with a method to obtain the potential of mean force (the weighted histogram analysis method) in which the free energy at any temperature can be evaluated from one or a few simulations. This method not only allows us to obtain the temperature dependence of free energy but it also has a built-in estimate for sampling errors. The temperature dependence of hydrophobic hydration at 20°C–80°C was successfully reproduced from two or four simulations.