What is theory behind free energy perturbation? Is it way too difficult to understand? Can someone explain it in simple terms.
Free energy perturbation is a free energy method, i.e. it allows one to calculate the difference in free energy between two states A and B, during a molecular simulation. Other, and possibly better-known free energy methods, include thermodynamic integration and umbrella sampling.
The idea behind the free energy perturbation method is that, if your states A and B are close enough, i.e. if they represent well-overlapping regions of phase space, you can get information about their free energy difference from one single molecular simulation in one of the states. The big gain of using a small perturbation is that you don't need to actually sample both A and B, because they're close enough.