ZDOCK: An initial‐stage protein‐docking algorithm

TLDR

Scoring functions are essential for accurate protein docking. The study introduces a new scoring function for the initial stage of unbound protein docking. The function integrates pairwise shape complementarity, desolvation, and electrostatics and is implemented in the FFT‑based ZDOCK algorithm available to academics. On a benchmark of 49 nonredundant cases, the new function outperforms three others, retaining at least one near‑native structure in 90 % of cases and averaging 52 near‑native hits per case, with remaining failures attributed to low affinity, backbone changes, and a bias toward concave pockets. © 2003 Wiley‑Liss, Inc.; published in Proteins 52:80–87.

Abstract

Abstract The development of scoring functions is of great importance to protein docking. Here we present a new scoring function for the initial stage of unbound docking. It combines our recently developed pairwise shape complementarity with desolvation and electrostatics. We compare this scoring function with three other functions on a large benchmark of 49 nonredundant test cases and show its superior performance, especially for the antibody‐antigen category of test cases. For 44 test cases (90% of the benchmark), we can retain at least one near‐native structure within the top 2000 predictions at the 6° rotational sampling density, with an average of 52 near‐native structures per test case. The remaining five difficult test cases can be explained by a combination of poor binding affinity, large backbone conformational changes, and our algorithm's strong tendency for identifying large concave binding pockets. All four scoring functions have been integrated into our Fast Fourier Transform based docking algorithm ZDOCK, which is freely available to academic users at http://zlab.bu.edu/∼rong/dock . Proteins 2003;52:80–87. © 2003 Wiley‐Liss, Inc.