The Fast Fourier Transform (FFT) correlation approach to protein-protein docking 
can evaluate the energies of billions of docked conformations on a grid if the 
energy is described in the form of a correlation function. Here, this 
restriction is removed, and the approach is efficiently used with pairwise 
interaction potentials that substantially improve the docking results. The basic 
idea is approximating the interaction matrix by its eigenvectors corresponding 
to the few dominant eigenvalues, resulting in an energy expression written as 
the sum of a few correlation functions, and solving the problem by repeated FFT 
calculations. In addition to describing how the method is implemented, we 
present a novel class of structure-based pairwise intermolecular potentials. The 
DARS (Decoys As the Reference State) potentials are extracted from structures of 
protein-protein complexes and use large sets of docked conformations as decoys 
to derive atom pair distributions in the reference state. The current version of 
the DARS potential works well for enzyme-inhibitor complexes. With the new 
FFT-based program, DARS provides much better docking results than the earlier 
approaches, in many cases generating 50% more near-native docked conformations. 
Although the potential is far from optimal for antibody-antigen pairs, the 
results are still slightly better than those given by an earlier FFT method. The 
docking program PIPER is freely available for noncommercial applications.