PIPER: FFT-based docking with pairwise potentials
PIPER performs exhaustive evaluation of an energy function in discretized 6D space of mutual orientations of two proteins. We sample 70,000 rotations which approximately correspond to sampling at every 5 degrees in the space of Euler angles. In the translational space the sampling is defined by the 1.2 Å grid cell size. The energy-like scoring function describing the receptor-ligand interactions is defined on this grid and is efficiently calculated using Fast Fourier transforms. Results are clustered with a 10 Å cube size, and one or several lowest energy translations for the given rotation are retained. Finally, results from different rotations are collected and sorted.
The novelty of the PIPER algorithm is that the scoring function includes an energy term of the form Epair = ΣiΣjεij, where εij is a pairwise interaction potential between atoms i and j. The key to the efficient use of this potential within the FFT framework is the eigenvalue-eigenvector decomposition of the interaction matrix. The complete scoring function is given as the sum of terms representing shape complementarity, electrostatic, and desolvation contributions, the latter described by the pairwise potential. We have shown that PIPER increases the number of near-native conformations in the top 1000 or 2000 structures relative to other FFT-based docking programs (Kozakov et al., 2006)
PIPER can be easily tested using our new server ClusPro 2.0, and it is freely available for noncommercial applications.