Predicting protein-protein interaction at the molecular level is a computationally intensive process. The Dock Proteins (ZDOCK) protocol in Discovery Studio is an automated initial-stage global search algorithm that fully explores the relative positions of the two proteins in the rotational and translational space, using the Fast Fourier Transform (FFT) correlation techniques.

The original ZDOCK scoring function is a geometrical measure based on the extent of shape complementarity between the two protein partners. The Pairwise Shape Complementarity (PSC) scoring function has proven to be effective in benchmark test cases using large set of protein complexes, and performed well in several rounds of the CAPRI community-wide experiment.

Subsequently, a more detailed energetics based scoring function ZRANK has been developed and tested for reranking the docked protein poses. ZRANK can quickly and effectively rerank the whole set of ZDOCK poses, the scoring function is made of a linear weighted sum of van der Waals attractive and repulsive energies, electrostatic short and long range attractive and repulsive energies calculated based on the CHARMM 19 polar hydrogen potential, and the desolvation energy calculated using the Pairwise Atomic Contact Energy (ACE) method. The ZRANK scoring function has been shown significantly improved the success rate of ZDOCK predictions across large set of benchmark cases.