PIPER: An FFT‐based protein docking program with pairwise potentials

Abstract

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.

Mechanism of ATPase-mediated Cu+ Export and Delivery to Periplasmic Chaperones

“…Bioinformatics Analysis-Homology modeling of EcCopA was performed using SWISS-MODEL software (25) ) was analyzed with ClusPro version 2.0 using standard parameters (26,27).…”

In silico and in vitro studies to elucidate the role of Cu2+ and galanthamine as the limiting step in the amyloid beta (1–42) fibrillation process

“…19 To obtain an Ab dimer (lowest free energy), two of the same monomers were used. The ClusPro2.0 server, one of the top performers at CAPRI (Critical Assessment of Predicted Interactions) round [13][14][15][16][17][18][19]20 was used to predict the possible structure of the oligomers. We submitted to ClusPro two monomers to obtain the dimer, which was used to dock with another monomer to form a trimer, and so forth; this process was performed until an Ab pentamer was formed.…”

“…Both structures have the minimal sequence able to form the oligomers. 18 Therefore, the protein-protein docking was first performed with two monomers of each structure to build a dimer (Fig. 7, Set 1, in blue).…”

Templates are available to model nearly all complexes of structurally characterized proteins

“…Template-free docking methods rely on the geometric and chemicalphysical complementarity of the protein surfaces (1), now often supplemented by statistical potentials (2,3), and subject to a variety of constraints (4). The template-free modeling can also be applied to prediction of domain-domain structures (5,6).…”