Improved ZDOCK Protein Docking Algorithm

The ZDOCK algorithm, which followed from initial efforts in FFT-based protein docking [18] (link), [19] (link) and was described in detail by Chen and Weng [10] (link), includes the following steps (not including the pre-processing step of marking surface atoms and atom types in PDB files). The terms “receptor” and “ligand” refer to the two input proteins, with the receptor generally being the larger protein or known to function as a receptor in vivo (e.g. an antibody in an antibody/antigen interaction).
ZD1. Center receptor coordinates at origin based on center of mass.ZD2. Center ligand coordinates at origin based on center of mass.ZD3. Select cubic grid size to contain centered molecules for FFT.ZD4. Discretize receptor, assigning scores to 3D grid(s) of complex numbers.
ZD5. Rotate input ligand to random orientation, if specified.
ZD6. Rotate ligand to Euler angles from uniformly distributed set, and discretize.
ZD7. Perform 3D FFT to compute convolution between ligand and receptor grids, and select top scoring position from the resultant grid.ZD8. Repeat steps 6–7 for a total of 3,600 ligand rotations (15° angular sampling) or 54,000 ligand rotations (6° angular sampling).
Here we present major improvements to ZDOCK's initial orientation and FFT procedures (bold steps above), while not modifying the discretization protocols that embody the ZDOCK scoring function. Previous ZDOCK versions and their scoring terms include: ZDOCK 1.3 [10] (link): Grid-based shape complementarity, atomic contact energy (ACE; [20] (link)), electrostatics: ZDOCK 2.1 [21] (link): Pairwise shape complementarity (PSC); ZDOCK 2.3 [14] (link): PSC, ACE, electrostatics; ZDOCK 3.0 [11] (link): PSC, interface atomic contact energy (IFACE), electrostatics.